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1. Prenatal and post-natal cost of small for gestational age infants: a national study

Author: Marzouk, Alicia, Filipovic-Pierucci, Antoine, Baud, Olivier, Tsatsaris, Vassilis, Ego, Anne, Charles, Marie-Aline, Goffinet, François, Evain-Brion, Danièle, Durand-Zaleski, Isabelle, PremUp Foundation, Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche Clinique en Economie de la santé d'Ile de France (URC Eco), Hôpital Robert Debré Paris, Hôpital Robert Debré, Service de Gynécologie et Obstétrique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Techniques pour l'Evaluation et la Modélisation des Actions de la Santé (TIMC-IMAG-ThEMAS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Equipe 6 : ORCHAD - Origines précoces de la santé du développement de l'enfant (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Hôpital Henri Mondor, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de recherche clinique en économie de la santé d'Ile-de-France (URC Eco), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), PREMUP foundation, a non-profit organisation. AM, OB, VT, MAC, FG, and IDZ are members of the PREMUP foundation. DEB is the director of the PREMUP foundation., Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Sorbonne Universités-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), AP-HP Hôpital universitaire Robert-Debré [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Universités-Université Paris Descartes - Paris 5 ( UPD5 ) -CHI Créteil-Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ), Unité de recherche clinique en économie de la santé d'Ile-de-France ( URC Eco ), Neuroprotection du Cerveau en Développement ( PROTECT ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiopathologie et Pharmacotoxicologie Placentaire Humaine ( U1139 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique ( CRESS - U1153 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables ( Inserm U1123 - ECEVE ), AP-HP Hôpital universitaire Robert-Debré [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), BMC, BMC, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Universités-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), and Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: Length of Stay/economics, Adult, Male, Diseases/economics/therapy, [SDV]Life Sciences [q-bio], Mothers, Mothers/statistics & numerical data, Gestational Age, Infant, Premature, Diseases, Database, Sex Factors, Pregnancy, Birth Weight, Humans, Economic cost, Obstetric/economics, Premature, reproductive and urinary physiology, ComputingMilieux_MISCELLANEOUS, ddc:618, [ SDV ] Life Sciences [q-bio], Health Policy, Infant, Newborn, Infant, Small for gestational age, Length of Stay, Newborn, Delivery, Obstetric, female genital diseases and pregnancy complications, [SDV] Life Sciences [q-bio], Perinatal Care, Cross-Sectional Studies, Infant, Small for Gestational Age, Costs and Cost Analysis, Small for Gestational Age, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Perinatal Care/economics, France, Morbidity, Prematurity, Delivery, Infant, Premature, Research Article
Abstract: International audience; AbstractBackgroundSmall for gestational age (SGA) infants are at increased risk for preterm birth morbidities as well as a range of adverse perinatal outcomes that result in part from associated premature birth. We sought to evaluate the costs of SGA versus appropriate for gestational age (AGA) infants in France from pregnancy through the first year of life and separate the contributions of prematurity from the contribution of foetal growth on costs.MethodsThis is a cross-sectional population-based study using national hospital discharge data from French public and private hospitals. SGA infants were defined as newborns with a birth weight below the 10th percentile of French intrauterine growth curves adjusted for foetal sex. AGA infants were defined as newborns with a birth weight between the 25th and the 75th. All births were selected between January 1st, 2011 and December 31st, 2011. Costs were calculated from the hospital perspective for both mothers and children using their diagnostic related group and the French national cost study. Hospital outcomes were extracted from the database and compared by gestational age and mode of delivery.ResultsOf 777,720 total births in 2011, 84,688 SGA births (10.9%) and 395,760 AGA births (50.8%) were identified. After adjustment for gestational age, the cost for an SGA infant was €2,783 higher than for an AGA infant. The total maternal and infant hospital cost of SGA in France was estimated at 23% the total cost for deliveries. The high cost is explained by higher complication rates, more frequent hospital readmissions and longer lengths of stay.ConclusionsBeing small for gestational age is an independent contributor to 1-year hospital costs for both mothers and infants.
Published: 2017

2. PPARγ controls pregnancy outcome through activation of EG-VEGF: new insights into the mechanism of placental development

Author: Wael Traboulsi, Aude Salomon, Valentina Onnis, Béatrice Desvergne, Cenzo Congiu, Mohamed Benharouga, Carine Winkler, Jean-Jacques Feige, Thierry Fournier, Sophie Brouillet, Qun-Yong Zhou, Pascale Hoffmann, Nadia Alfaidy, Vanessa Garnier, Biologie du Cancer et de l'Infection ( BCI - UMR S1036 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Grenoble Alpes ( UGA ), Department of Life and Environmental Sciences, University of Cagliari, Physiopathologie et Pharmacotoxicologie Placentaire Humaine ( U1139 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), PremUp Foundation, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Universités-Université Paris Descartes - Paris 5 ( UPD5 ) -CHI Créteil-Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ), Center for Integrative Genomics - Institute of Bioinformatics, Génopode ( CIG ), University of Lausanne, Département de Gynécologie, Obstétrique et Médecine de la Reproduction, CHU Grenoble, Department of Pharmacology [Irvine], University of California [Irvine] ( UCI ), Laboratoire de Chimie et Biologie des Métaux ( LCBM - UMR 5249 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), University of California [Irvine] (UCI), University of California-University of California, Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Universités-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), and Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)
Subjects: Male, Pyridines, Physiology, Placenta, Endocrinology, Diabetes and Metabolism, Peroxisome proliferator-activated receptor, ANGIOGENESIS, HUMAN FETOPLACENTAL VASCULOGENESIS, Mice, trophoblast invasion, Pregnancy, Cricetinae, human pregnancy, MOLECULAR CHARACTERIZATION, Receptor, [ SDV.MHEP.GEO ] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Cells, Cultured, chemistry.chemical_classification, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Pregnancy Outcome, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [ SDV.BDLR ] Life Sciences [q-bio]/Reproductive Biology, medicine.anatomical_structure, embryonic structures, Benzamides, Female, EXPRESSION, Transcriptional Activation, medicine.medical_specialty, PATHOLOGICAL IMPLICATIONS, Mice, Transgenic, Biology, Rosiglitazone, endocrine gland-derived vascular endothelial growth factor, PROTEIN-COUPLED RECEPTORS, In vivo, Physiology (medical), Internal medicine, medicine, Animals, Humans, Embryo Implantation, OXYGEN REGULATION, Placentation, Trophoblast, Prokineticin receptor 1, Embryo, Mammalian, EXTRAVILLOUS TROPHOBLASTS, peroxisome proliferator-activated receptor-gamma knockout, PPAR gamma, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Endocrinology, chemistry, ENDOTHELIAL GROWTH-FACTOR, CELLS, Thiazolidinediones, Vascular Endothelial Growth Factor, Endocrine-Gland-Derived, Ex vivo
Abstract: PPARγ-deficient mice die at E9.5 due to placental abnormalities. The mechanism by which this occurs is unknown. We demonstrated that the new endocrine factor EG-VEGF controls the same processes as those described for PPARγ, suggesting potential regulation of EG-VEGF by PPARγ. EG-VEGF exerts its functions via prokineticin receptor 1 (PROKR1) and 2 (PROKR2). This study sought to investigate whether EG-VEGF mediates part of PPARγ effects on placental development. Three approaches were used: 1) in vitro, using human primary isolated cytotrophoblasts and the extravillous trophoblast cell line (HTR-8/SVneo); 2) ex vivo, using human placental explants ( n = 46 placentas); and 3) in vivo, using gravid wild-type PPARγ+/− and PPARγ−/− mice. Major processes of placental development that are known to be controlled by PPARγ, such as trophoblast proliferation, migration, and invasion, were assessed in the absence or presence of PROKR1 and PROKR2 antagonists. In both human trophoblast cell and placental explants, we demonstrated that rosiglitazone, a PPARγ agonist, 1) increased EG-VEGF secretion, 2) increased EG-VEGF and its receptors mRNA and protein expression, 3) increased placental vascularization via PROKR1 and PROKR2, and 4) inhibited trophoblast migration and invasion via PROKR2. In the PPARγ−/− mouse placentas, EG-VEGF levels were significantly decreased, supporting an in vivo control of EG-VEGF/PROKRs system during pregnancy. The present data reveal EG-VEGF as a new mediator of PPARγ effects during pregnancy and bring new insights into the fine mechanism of trophoblast invasion.
Published: 2015

3. Bacterial infection in compensated viral cirrhosis impairs 5-year survival (ANRS CO12 CirVir prospective cohort)

Author: Nahon, Pierre, Lescat, Mathilde, Layese, Richard, Bourcier, Valérie, Talmat, Nabila, Allam, Setty, Marcellin, Patrick, Guyader, Dominique, Pol, Stanislas, Larrey, Dominique, de Lédinghen, Victor, Ouzan, Denis, Zoulim, Fabien, Roulot, Dominique, Tran, Albert, Bronowicki, Jean-Pierre, Zarski, Jean-Pierre, Goria, Odile, Calès, Paul, Peron, Jean-Marie, Alric, Laurent, Bourlière, Marc, Mathurin, Philippe, Blanc, Jean-Frederic, Abergel, Armand, Serfaty, Lawrence, Mallat, Ariane, Grangé, Jean-Didier, Attali, Pierre, Bacq, Yannick, Wartelle, Claire, Dao, Thong, Benhamou, Yves, Pilette, Christophe, Silvain, Christine, Christidis, Christos, Capron, Dominique, Bernard-Chabert, Brigitte, Hillaire, Sophie, Di Martino, Vincent, Trinchet, Jean-Claude, Moreau, Richard, Roudot-Thoraval, Françoise, Cirvir Group, Anrs Co12, Service d'hépato-gastroentérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [AP-HP], Service d'Hépato-gastroentérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Department of hepatology, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hépatologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Cellules souches normales et cancéreuses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Pôle Digestif, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), CHU Rouen, Normandie Université (NU), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Hepato-gastro-enterology, Toulouse University hospital, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service d'hépato-gastro-entérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital Huriez-Université de Lille, Inserm, UMR-1053, Université de Bordeaux, Bordeaux, F-33076, France, Centre hospitalier universitaire de Bordeaux, Department of Hepatology, Hôpital Saint-André, Bordeaux, F-33076, France, Centre Hospitalier Universitaire Estaing, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service d'hépato-gastro-entérologie [APHP Henri Mondor], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Service de gastro-entérologie [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Hépatogastroentérologie, CHU Amiens-Picardie, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut Arnault Tzanck, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Saint-André, Hôpital Hôtel-Dieu de Clermont-Ferrand, CHU Clermont-Ferrand, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Tenon [AP-HP], CHU Trousseau [APHP], Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Le Mans (CH Le Mans), Institut mutualiste Monsouris (IMM), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Foch [Suresnes], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes (UGA)-CHU Grenoble, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP), Centre de recherche biomédicale Bichat-Beaujon ( CRB3 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiopathologie et Pharmacotoxicologie Placentaire Humaine ( U1139 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Jean Verdier, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Jean Verdier, Centre de recherche sur l'Inflammation ( CRI ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Cochin [AP-HP], Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -CHU Saint-Eloi, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hospices Civils de Lyon ( HCL ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Centre méditérannéen de médecine moléculaire ( C3M ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Nice-Hôpital l'Archet, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques ( HIFIH ), Université d'Angers ( UA ), Pharmacochimie et Pharmacologie Pour le Développement ( PHARMA-DEV ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique ( CNRS ), Assistance Publique - Hôpitaux de Marseille ( APHM ), CHU Saint-Antoine [APHP], Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse, Service de gastro-entérologie, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Service d'Hépato-Gastro-Enterologie et Nutrition [Caen], Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen, Mobilités : Vieillissement, Pathologie, Santé ( COMETE ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Liver Cirrhosis, Male, Cirrhosis, Gastroenterology, Severity of Illness Index, 0302 clinical medicine, Risk Factors, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Cause of Death, Medicine, Cumulative incidence, Prospective Studies, Prospective cohort study, Coinfection, Incidence, Liver Neoplasms, Hepatitis C, Bacterial Infections, Hepatitis B, Middle Aged, Prognosis, 3. Good health, Survival Rate, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030220 oncology & carcinogenesis, Urinary Tract Infections, HEPATITIS C, 030211 gastroenterology & hepatology, Female, France, Liver cancer, Viral hepatitis, Adult, medicine.medical_specialty, Peritonitis, 03 medical and health sciences, Hepatitis B, Chronic, Internal medicine, Humans, Survival rate, business.industry, cirrhosis, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Pneumonia, Hepatitis C, Chronic, medicine.disease, BACTERIAL INFECTION, Immunology, business, Liver Failure
Abstract: International audience; OBJECTIVE: To assess incidence and prognostic significance of bacterial infections (BIs) occurring in compensated viral cirrhosis. DESIGN: This prospective study involved 35 French centres. Inclusion criteria were biopsy-proven HCV or HBV cirrhosis, Child-Pugh A and no previous hepatic complications. Cumulative incidence (CumI) of events was estimated in a competing risks framework. RESULTS: 1672 patients were enrolled (HCV 1323, HBV 318, HCV-HBV 31). During a median follow-up of 43 months, 234 BIs occurred in 171 patients (5 year CumI: 12.9%), among whom 14.6% had septic shock. Main localisations included the urinary tract (27.4%), lung (25.2%) and peritoneum (10.7%) (other, 86 (36.7%)). Most BIs occurred as a first event prior to liver decompensation (n=140, 81.8%) and were community-acquired (CA, 84.2%). The risk of BI was higher in patients with HCV than in patients with HBV (5 year CumI: 15.2% vs 5.5%, p=0.0008). Digestive localisation, concomitant interferon-based treatment, isolation of resistant bacteria and non-CA BIs were associated with lowest probability of resolution. The occurrence of a first BI impaired survival in patients infected with HCV (5 year survival: 60.2% vs 90.4%, p\textless0.001) and patients infected with HBV (5 year survival: 69.2% vs 97.6%, p\textless0.001). BIs represented the third cause of death (14.1%) after liver failure and liver cancer. BI risk factors comprised older age, lower albumin, proton pump inhibitor intake and absence of virological eradication/control. CONCLUSION: BI mostly occurs as a first complication and represents a turning point in the course of compensated viral cirrhosis. Its occurrence impacts long-term prognosis and may define a subgroup of patients in whom adaptation of management is warranted
Published: 2017

4. Angiogenin Expression during Early Human Placental Development; Association with Blood Vessel Formation

Author: Séverine A. Degrelle, Jean-Louis Frendo, Josette Badet, Danièle Evain-Brion, Jean Guibourdenche, Nadine Pavlov, Badet, Josette, Université de Lorraine (UL), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de biologie du développement (CBD), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Service d'endocrinologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), PremUp Foundation, Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale, Association de la Recherche sur le Cancer, Ligue contre le Cancer, Novo Nordisk Pharmaceutics, Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Lorraine ( UL ), Physiopathologie et Pharmacotoxicologie Placentaire Humaine ( U1139 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de biologie du développement ( CBD ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), and Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Universités-Université Paris Descartes - Paris 5 ( UPD5 ) -CHI Créteil-Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 )
Subjects: CD31, medicine.medical_specialty, Article Subject, placenta, Angiogenin, Angiogenesis, Primary Cell Culture, lcsh:Medicine, Biology, General Biochemistry, Genetics and Molecular Biology, vasculogenesis, angiogenesis, chemistry.chemical_compound, Vasculogenesis, Pregnancy, Internal medicine, Placenta, [SDV.BDD] Life Sciences [q-bio]/Development Biology, medicine, Humans, [ SDV.BDD ] Life Sciences [q-bio]/Development Biology, development, [SDV.BDD]Life Sciences [q-bio]/Development Biology, In Situ Hybridization, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, General Immunology and Microbiology, lcsh:R, Decidua, Endothelial Cells, Gene Expression Regulation, Developmental, Trophoblast, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Ribonuclease, Pancreatic, General Medicine, trophoblast, Placentation, Trophoblasts, Cell biology, Vascular endothelial growth factor, [ SDV.BDLR ] Life Sciences [q-bio]/Reproductive Biology, medicine.anatomical_structure, Endocrinology, chemistry, embryonic structures, Blood Vessels, Female, Chorionic Villi, angiogenin, Research Article
Abstract: The placenta is a transient organ essential for fetal development. During human placental development, chorionic villi grow in coordination with a large capillary network resulting from both vasculogenesis and angiogenesis. Angiogenin is one of the most potent inducers of neovascularisation in experimental modelsin vivo. We and others have previously mapped angiogenin expression in the human term placenta. Here, we explored angiogenin involvement in early human placental development. We studied, angiogenin expression byin situhybridisation and/or by RT-PCR in tissues and primary cultured trophoblastic cells and angiogenin cellular distribution by coimmunolabelling with cell markers: CD31 (PECAM-1), vascular endothelial cadherin (VE-cadherin), vascular endothelial growth factor receptor-2 (VEGF-R2), Tie-2, von Willebrand factor, CD34, erythropoeitin receptor (Epo-R), alpha-smooth muscle actin, CD45, cytokeratin 7, and Ki-67. Extravillous and villous cytotrophoblasts, isolated and differentiatedin vitro, expressed and secreted angiogenin. Angiogenin was detected in villous trophoblastic layers, and structured and nascent fetal vessels. In decidua, it was expressed by glandular epithelial cells, vascular cells and macrophages. The observed pattern of angiogenin expression is compatible with a role in blood vessel formation and in cross-talk between trophoblasts and endothelial cells. In view of angiogenin properties, we suggest that angiogenin may participate in placental vasculogenesis and organogenesis.
Published: 2014

5. Computational Fluid Dynamic Simulations of Maternal Circulation: Wall Shear Stress in the Human Placenta and Its Biological Implications

Author: Abdul I. Barakat, Mrugank Bhatt, L. J. Salomon, Philippe Deloron, Edouard Lecarpentier, Gwladys Bertin, Vassilis Tsatsaris, Thierry Fournier, Benjamin Deloison, Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), PremUp Foundation, Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gynécologie et Obstétrique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), DHU Risques Et Grossesse, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'hydrodynamique (LadHyX), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Fédération pour la recherche en explorations et thérapeutiques innovantes in utéro (FETUS - EA 7328), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et Pharmacotoxicologie Placentaire Humaine ( U1139 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Universités-Université Paris Descartes - Paris 5 ( UPD5 ) -CHI Créteil-Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'hydrodynamique ( LadHyX ), École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ), Mère et enfant face aux infections tropicales ( MERIT - UMR_D 216 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut de Recherche pour le Développement ( IRD ), Fédération pour la recherche en explorations et thérapeutiques innovantes in utéro ( FETUS - EA 7328 ), Université Paris Descartes - Paris 5 ( UPD5 ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Universités-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X), Mère et enfant face aux infections tropicales (MERIT - UMR_D 216), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Embryology, Erythrocytes, Physiology, Placenta, Maternal Health, Hemodynamics, lcsh:Medicine, Diagnostic Radiology, 0302 clinical medicine, Pregnancy, Animal Cells, Red Blood Cells, Blood Flow, Medicine and Health Sciences, [PHYS.MECA.MEFL]Physics [physics]/Mechanics [physics]/Fluid mechanics [physics.class-ph], lcsh:Science, Shear Stresses, 030219 obstetrics & reproductive medicine, Multidisciplinary, [PHYS.MECA.MEFL]Physics [physics]/Mechanics [physics]/Mechanics of the fluids [physics.class-ph], Radiology and Imaging, Physics, [ PHYS.MECA.MEFL ] Physics [physics]/Mechanics [physics]/Mechanics of the fluids [physics.class-ph], Obstetrics and Gynecology, Classical Mechanics, Intervillous space, Hematology, Arteries, Magnetic Resonance Imaging, Body Fluids, Circulation (fluid dynamics), medicine.anatomical_structure, Blood, embryonic structures, Physical Sciences, cardiovascular system, Mechanical Stress, Female, Anatomy, Cellular Types, Shear Strength, Blood Flow Velocity, circulatory and respiratory physiology, Research Article, Imaging Techniques, Research and Analysis Methods, Models, Biological, Andrology, 03 medical and health sciences, Syncytiotrophoblast, Diagnostic Medicine, medicine, Shear stress, Humans, Computer Simulation, Blood Cells, lcsh:R, Reproductive System, Biology and Life Sciences, Blood flow, Cell Biology, medicine.disease, 030104 developmental biology, Immunology, Cardiovascular Anatomy, Hydrodynamics, Women's Health, Blood Vessels, lcsh:Q, Stress, Mechanical, Developmental Biology
Abstract: Introduction In the human placenta the maternal blood circulates in the intervillous space (IVS). The syncytiotrophoblast (STB) is in direct contact with maternal blood. The wall shear stress (WSS) exerted by the maternal blood flow on the STB has not been evaluated. Our objective was to determine the physiological WSS exerted on the surface of the STB during the third trimester of pregnancy. Material and Methods To gain insight into the shear stress levels that the STB is expected to experience in vivo, we have formulated three different computational models of varying levels of complexity that reflect different physical representations of the IVS. Computations of the flow fields in all models were performed using the CFD module of the finite element code COMSOL Multi-physics 4.4. The mean velocity of maternal blood in the IVS during the third trimester was measured in vivo with dynamic MRI (0.94 +/- 0.14 mm.s(-1)). To investigate if the in silico results are consistent with physiological observations, we studied the cytoadhesion of human parasitized (Plasmodium falciparum) erythrocytes to primary human STB cultures, in flow conditions with different WSS values. Results The WSS applied to the STB is highly heterogeneous in the IVS. The estimated average values are relatively low (0.5 +/- 0.2 to 2.3 +/- 1.1 dyn.cm(-2)). The increase of WSS from 0.15 to 5 dyn.cm(-2) was associated with a significant decrease of infected erythrocyte cytoadhesion. No cytoadhesion of infected erythrocytes was observed above 5 dyn.cm(-2) applied for one hour. Conclusion Our study provides for the first time a WSS estimation in the maternal placental circulation. In spite of high maternal blood flow rates, the average WSS applied at the surface of the chorionic villi is low (
Published: 2016

6. An EG-VEGF-dependent decrease in homeobox gene NKX3.1 contributes to cytotrophoblast dysfunction: a possible mechanism in human fetal growth restriction

Author: Nadia Alfaidy, Frédéric Goffin, Vassilis Tsatsaris, Jean-Jacques Feige, Carine Munaut, Anita Pratt, Bill Kalionis, Padma Murthi, Mohamed Benharouga, Anthony J. Borg, Sophie Brouillet, Thierry Fournier, Department of Obstetrics and Gynaecology [Melbourne], Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne-Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, Department of Perinatal Medicine, Royal Women's Hospital, Monash University [Clayton], Department of Medicine, Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Pôle Couple-Enfant, Département de Génétique et Procréation, Laboratoire de Biologie des Tumeurs et du Développement), Université de Liège, La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maternité Port-Royal [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), PremUp Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Biologie des Métaux (BioMet), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Invasion mechanisms in angiogenesis and cancer (IMAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), laboratory of clinical investigation III, University of Geneva [Switzerland], Department of Obstetrics and Gynaecology, University of Melbourne, Biologie du Cancer et de l'Infection ( BCI - UMR S1036 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Grenoble Alpes ( UGA ), CHU de Grenoble, Hôpital Couple-Enfant, Département de Génétique et Procréation, La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus ( UMR_S 767 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Laboratoire de Chimie et Biologie des Métaux ( LCBM - UMR 5249 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -CHI Créteil-Université Paris Descartes - Paris 5 ( UPD5 ) -Sorbonne Universités-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiopathologie et Pharmacotoxicologie Placentaire Humaine ( U1139 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Sorbonne Universités-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Protein Structure, Quaternary, MESH: Cricetinae, Placental insufficiency, Biology, Cystic fibrosis, Andrology, MESH: Protein Structure, Tertiary, chemistry.chemical_compound, Syncytiotrophoblast, MESH: Protein Stability, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, medicine, Quaternary structure, MESH: Animals, CFTR, Membrane stability, [ SDV.MHEP.GEO ] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, NBD2, Molecular Biology, Gene, Genetics (clinical), MESH: Cystic Fibrosis Transmembrane Conductance Regulator, Messenger RNA, MESH: Humans, Cytotrophoblast, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Trophoblast, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Articles, medicine.disease, Molecular biology, MESH: Cell Line, Vascular endothelial growth factor, [ SDV.BDLR ] Life Sciences [q-bio]/Reproductive Biology, medicine.anatomical_structure, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, chemistry, [ SDV.BDD.EO ] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, embryonic structures, Molecular Medicine, Homeobox, Dimerization, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: Cell Membrane
Abstract: International audience; Idiopathic fetal growth restriction (FGR) is frequently associated with placental insufficiency. Previous reports have provided evidence that endocrine gland-derived vascular endothelial growth factor (EG-VEGF), a placental secreted protein, is expressed during the first trimester of pregnancy, controls both trophoblast proliferation and invasion, and its increased expression is associated with human FGR. In this study, we hypothesize that EG-VEGF-dependent changes in placental homeobox gene expressions contribute to trophoblast dysfunction in idiopathic FGR. The changes in EG-VEGF-dependent homeobox gene expressions were determined using a homeobox gene cDNA array on placental explants of 8-12 wks gestation after stimulation with EG-VEGF in vitro for 24 h. The homeobox gene array identified a greater-than-five-fold increase in HOXA9, HOXC8, HOXC10, HOXD1, HOXD8, HOXD9 and HOXD11, while NKX 3.1 showed a greater-than-two-fold decrease in mRNA expression compared with untreated controls. Homeobox gene NKX3.1 was selected as a candidate because it is a downstream target of EG-VEGF and its expression and functional roles are largely unknown in control and idiopathic FGR-affected placentae. Real-time PCR and immunoblotting showed a significant decrease in NKX3.1 mRNA and protein levels, respectively, in placentae from FGR compared with control pregnancies. Gene inactivation in vitro using short-interference RNA specific for NKX3.1 demonstrated an increase in BeWo cell differentiation and a decrease in HTR-8/SVneo proliferation. We conclude that the decreased expression of homeobox gene NKX3.1 downstream of EG-VEGF may contribute to the trophoblast dysfunction associated with idiopathic FGR pregnancies.
Published: 2015

7. Discriminative imaging of maternal and fetal blood flow within the placenta using ultrafast ultrasound

Author: Osmanski, Bruno-Felix, Lecarpentier, Edouard, Montaldo, Gabriel, Tsatsaris, Vassilis, Chavatte-Palmer, Pascale, Tanter, Mickael, Institut Langevin - Ondes et Images (UMR7587) (IL), Sorbonne Université (SU)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS), Physique des ondes pour la médecine, Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Obstetrics and Gynecology Unit, Université Paris Descartes - Paris 5 (UPD5), PremUp Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), DHU Risques Et Grossesse, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Foundation PremUp and the Region Ile de France, Laboratory of Excellence ANR-10-LABX-24), Institut Langevin ondes et images, Centre National de la Recherche Scientifique (CNRS)-ESPCI ParisTech-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Universités-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Biologie du développement et reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique ( CNRS ) -ESPCI ParisTech-Université Paris Diderot - Paris 7 ( UPD7 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Physiopathologie et Pharmacotoxicologie Placentaire Humaine ( U1139 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Universités-Université Paris Descartes - Paris 5 ( UPD5 ) -CHI Créteil-Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Biologie du développement et reproduction ( BDR ), Institut National de la Recherche Agronomique ( INRA ) -Ecole Nationale Vétérinaire d'Alfort-Centre National de la Recherche Scientifique ( CNRS ), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), and HAL UPMC, Gestionnaire
Subjects: Placenta, ultrasonographie, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Ultrasonography, Prenatal, Article, mère, Fetus, Imaging, Three-Dimensional, Pregnancy, Image Interpretation, Computer-Assisted, Biologie de la reproduction, Image Processing, Computer-Assisted, Animals, [ SDV.MHEP.GEO ] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Reproductive Biology, Fetal Growth Retardation, Biologie du développement, circulation sanguine, Ultrasonography, Doppler, Development Biology, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Disease Models, Animal, Regional Blood Flow, Female, Rabbits, fœtus, Algorithms
Abstract: Remerciements à INRA UCEA et CR2i; International audience; Being able to map accurately placental blood flow in clinics could have major implications in the diagnosis and follow-up of pregnancy complications such as intrauterine growth restriction (IUGR). Moreover, the impact of such an imaging modality for a better diagnosis of placental dysfunction would require to solve the unsolved problem of discriminating the strongly intricated maternal and fetal vascular networks. However, no current imaging modality allows both to achieve sufficient sensitivity and selectivity to tell these entangled flows apart. Although ultrasound imaging would be the clinical modality of choice for such a problem, conventional Doppler echography both lacks of sensibility to detect and map the placenta microvascularization and a concept to discriminate both entangled flows. In this work, we propose to use an ultrafast Doppler imaging approach both to map with an enhanced sensitivity the small vessels of the placenta (~100 μm) and to assess the variation of the Doppler frequency simultaneously in all pixels of the image within a cardiac cycle. This approach is evaluated in vivo in the placenta of pregnant rabbits: By studying the local flow pulsatility pixel per pixel, it becomes possible to separate maternal and fetal blood in 2D from their pulsatile behavior. Significance Statement: The in vivo ability to image and discriminate maternal and fetal blood flow within the placenta is an unsolved problem which could improve the diagnosis of pregnancy complications such as intrauterine growth restriction or preeclampsia. To date, no imaging modality has both sufficient sensitivity and selectivity to discriminate these intimately entangled flows. We demonstrate that Ultrafast Doppler ultrasound method with a frame rate 100x faster than conventional imaging solves this issue. It permits the mapping of small vessels of the placenta (~100 μm) in 2D with an enhanced sensitivity. By assessing pixel-per-pixel pulsatility within single cardiac cycles, it achieves maternal and fetal blood flow discrimination.
Published: 2015

8. Human Cytomegalovirus Modifies Placental Small Extracellular Vesicle Composition to Enhance Infection of Fetal Neural Cells In Vitro

Author: Mathilde Bergamelli, Hélène Martin, Yann Aubert, Jean-Michel Mansuy, Marlène Marcellin, Odile Burlet-Schiltz, Ilse Hurbain, Graça Raposo, Jacques Izopet, Thierry Fournier, Alexandra Benchoua, Mélinda Bénard, Marion Groussolles, Géraldine Cartron, Yann Tanguy Le Gac, Nathalie Moinard, Gisela D’Angelo, Cécile E. Malnou, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pathologies et épithéliums : prévention, innovation, traitements, évaluation (UR 4267) (PEPITE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Institut de pharmacologie et de biologie structurale (IPBS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des cellules souches pour le traitement et l'étude des maladies monogéniques (I-STEM), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Développement Embryonnaire, Fertilité et Environnement (DEFE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Physiopathologie et pharmacotoxicologie placentaire humaine : Microbiote pré & post natal (3PHM - UMR-S 1139), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), ANR-10-INBS-0008,ProFI,Infrastructure Française de Protéomique(2010), and ANR-11-LABX-0038,CelTisPhyBio,Des cellules aux tissus: au croisement de la Physique et de la Biologie(2011)
Subjects: Proteomics, placenta, [SDV]Life Sciences [q-bio], Cytomegalovirus, cytotrophoblast, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, hCMV, congenital infection, Infectious Diseases, extracellular vesicles, Pregnancy, Virology, Cytomegalovirus Infections, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Humans, Female
Abstract: International audience; Although placental small extracellular vesicles (sEVs) are extensively studied in the context of pregnancy, little is known about their role during viral congenital infection, especially at the beginning of pregnancy. In this study, we examined the consequences of human cytomegalovirus (hCMV) infection on sEVs production, composition, and function using an immortalized human cytotrophoblast cell line derived from first trimester placenta. By combining complementary approaches of biochemistry, electron microscopy, and quantitative proteomic analysis, we showed that hCMV infection increases the yield of sEVs produced by cytotrophoblasts and modifies their protein content towards a potential proviral phenotype. We further demonstrate that sEVs secreted by hCMV-infected cytotrophoblasts potentiate infection in naive recipient cells of fetal origin, including human neural stem cells. Importantly, these functional consequences are also observed with sEVs prepared from an ex vivo model of infected histocultures from early placenta. Based on these findings, we propose that placental sEVs could be important actors favoring viral dissemination to the fetal brain during hCMV congenital infection.
Published: 2022

9. Gut microbiota alterations in critically ill older patients: a multicenter study

Author: Mesa Victoria, Valdés-Duque Beatriz Elena, Giraldo-Giraldo Nubia Amparo, Jailler-R Ana María, Giraldo-Villa Adriana, Acevedo-Castaño Irene, Yepes-M Mónica Alejandra, Barbosa-Barbosa Janeth, Agudelo-Ochoa Gloria María, Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institución Universitaria Colegio Mayor - Medellín [Antioquia, Colombia] (IUCMM), Hospital San Vicente Fundación - Rionegro [Antioquia, Colombia] (HSVFR), Hospital Pablo Tobón Uribe - Medellín [Antioquia, Colombie] (HPTUM), Hospital General de Medellín [Antioquia, Colombia] (HGM), Hospital San Vicente Fundación - Medellín [Antioquia, Colombia] (HSVFM), Clínica Las Américas - Medellín [Antioquia, Colombia] (CLAM), and Malbec, Odile
Subjects: Critical Illness, Microbiota, [SDV]Life Sciences [q-bio], Gut microbiota, Middle Aged, digestive system, Anti-Bacterial Agents, Gastrointestinal Microbiome, [SDV] Life Sciences [q-bio], Feces, RNA, Ribosomal, 16S, Older adults, Sepsis, ICU, Humans, Dysbiosis, Geriatrics and Gerontology, Critically ill, Aged
Abstract: Background Aging generates changes in the gut microbiota, affecting its functionality. Little is known about gut microbiota in critically ill older adults. The objective of this study was to describe the profile of gut microbiota in a cohort of critically ill older adults. Methods This observational study was conducted in five health institutions. Over a 6-month study period, critically ill patients over 18 years old who were admitted to the intensive care unit were enrolled. Fecal microbiota profiles were determined from 155 individuals, over 60 years old (n = 72) and under 60 years old (n = 83). Gut microbiota was analyzed by sequencing the V3-V4 region of the 16S rRNA gene. Alpha and beta diversity, operational taxonomic units and the interaction of gut microbiota with variables under study were analyzed. Amplicon sequence variants (ASVs) specifically associated with age were recovered by including gender, discharge condition, BMI, ICU stay and antibiotics as covariates in a linear mixed model. Results In older adults, sepsis, malnutrition, antibiotic prescription and severity (APACHE and SOFA scores) were higher than in the group under 60 years of age. Alpha diversity showed lower gut microbiota diversity in those over 60 years of age (p p = 0.038). The microbiota of the adults under 60 years old showed greater abundance of Murdochiella, Megasphaera, Peptoniphilus and Ezakiella, whereas those over 60 years old Escherichia-Shigella and Hungatella were more abundant. Conclusion The gut microbial community was altered by different factors; however, age significantly explained the variability in critically ill patients. A lower presence of beneficial genera and a higher abundance of pathogens was observed in adults over 60 years old.
Published: 2022

10. Placental Models for Evaluation of Nanocarriers as Drug Delivery Systems for Pregnancy Associated Disorders

Author: Louise Fliedel, Khair Alhareth, Nathalie Mignet, Thierry Fournier, Karine Andrieux, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and dhotel, helene
Subjects: [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, pregnancy-associated disorders, placenta, nanocarriers, Medicine (miscellaneous), experimental models, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, General Biochemistry, Genetics and Molecular Biology
Abstract: International audience; Pregnancy-associated disorders affect around 20% of pregnancies each year around the world. The risk associated with pregnancy therapeutic management categorizes pregnant women as “drug orphan” patients. In the last few decades, nanocarriers have demonstrated relevant properties for controlled drug delivery, which have been studied for pregnancy-associated disorders. To develop new drug dosage forms it is mandatory to have access to the right evaluation models to ensure their usage safety and efficacy. This review exposes the various placental-based models suitable for nanocarrier evaluation for pregnancy-associated therapies. We first review the current knowledge about nanocarriers as drug delivery systems and how placenta can be used as an evaluation model. Models are divided into three categories: in vivo, in vitro, and ex vivo placental models. We then examine the recent studies using those models to evaluate nanocarriers behavior towards the placental barrier and which information can be gathered from these results. Finally, we propose a flow chart on the usage and the combination of models regarding the nanocarriers and nanoparticles studied and the intended therapeutic strategy
Published: 2022

11. Freeze-dried fecal samples are biologically active after long-lasting storage and suited to fecal microbiota transplantation in a preclinical murine model of Clostridioides difficile infection

Author: Christine Charrueau, Jérémy Augustin, Nathalie Kapel, Camille Mayeur, Anne-Judith Waligora-Dupriet, Morgane Modoux, Johanne Delannoy, Thierry Meylheuc, Francisca Joly, Céline Cuinat, Muriel Thomas, Julie Reygner, Véronique Robert, Ioannis Nicolis, Aurélie Mauras, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), AgroParisTech, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and ORANGE, Colette
Subjects: 0301 basic medicine, Time Factors, Administration, Oral, RC799-869, CLOSTRIDIUM-DIFFICILE, fecal microbiota transplant, Feces, Mice, fluids and secretions, 0302 clinical medicine, Freezing, INFECTION, pre-clinical model, Biological Specimen Banks, INDUCTION, Gastroenterology, Biological activity, MOUSE MODEL, Diseases of the digestive system. Gastroenterology, Fecal Microbiota Transplantation, 3. Good health, Treatment Outcome, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, ULCERATIVE-COLITIS, 030211 gastroenterology & hepatology, Microbiology (medical), Long lasting, Capsules, Biology, Microbiology, 03 medical and health sciences, Animals, Germ-Free Life, FROZEN, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Bacteria, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, REMISSION, Fecal bacteriotherapy, Fatty Acids, Volatile, EFFICACY, freeze-dried microbiota, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Gastrointestinal Microbiome, Disease Models, Animal, Freeze Drying, 030104 developmental biology, Murine model, clostridioides difficile, Research Paper/Report, Clostridium Infections, frozen microbiota, Clostridioides
Abstract: International audience; Fecal microbiota transplantation is now recommended for treating recurrent forms ofClostridioides difficileinfection. Recent studies have reported protocols using capsules of either frozen or freeze-dried stool allowing oral administration in in- and out-patient settings. However, a central question remains the viability, engraftment, and efficacy of the microbiome over time during storage life. This study shows that both the freeze-drying and freezing procedures for fecal samples allowed preserving viability, short-chain fatty acids concentration, and anti-Clostridioides difficileproperties of microbiota without significant alteration after storage for 12 months. Fecal transplantation with freeze-dried microbiota allowed engraftment of microbiota leading to clearance ofClostridioides difficileinfection in a preclinical murine model with a survival rate of 70%versus53-60% in mice treated with frozen inocula, and 20% in the untreated group. Moreover, the freeze-dried powder can be used to fill oral hard capsules using a very low amount (0.5%) of glidant excipient, allowing oral formulation. Altogether, this study showed that freeze-dried inocula can be used for the treatment ofClostridioides difficileinfection with long-lasting stability of the fecal microbiota. This formulation facilitates biobanking and allows the use of hard capsules, an essential step to simplify patient access to treatment.
Published: 2020

12. Irreversible inhibitors of the proline racemase unveil innovative mechanism of action as antibacterial agents against Clostridioides difficile

Author: Cécile Gateau, Guilherme D. Melo, Philippe Uriac, Olivier Tasseau, Jacques Renault, Arnaud Blondel, Nicolas Gouault, Frédéric Barbut, Paola Minoprio, Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology, Institut Pasteur [Paris], Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Processus infectieux à Trypanosomatidés - Trypanosomatids Infectious Processes, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Bioinformatique structurale - Structural Bioinformatics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Carnot Pasteur Microbes & Santé CARNOT/MS (ANR-16-CARN-0023-01 - non référencé dans AuréHAL), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Carnot Pasteur Microbes & Santé CARNOT/MS (ARN-16-CARN-0023-01 - non référencé dans AuréHAL)
Subjects: Pharmacology, 0303 health sciences, Proline, 010405 organic chemistry, Clostridioides difficile, enzyme inhibitors, structure-activity relationship, Organic Chemistry, 01 natural sciences, Biochemistry, 3. Good health, 0104 chemical sciences, Anti-Bacterial Agents, 03 medical and health sciences, antibacterial, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, proline racemase, Drug Discovery, parasitic diseases, Molecular Medicine, [CHIM]Chemical Sciences, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Amino Acid Isomerases
Abstract: International audience; Proline racemases (PRAC), catalyzing the l-proline and d-proline interconversion, are essential factors in eukaryotic pathogens such as Trypanosoma cruzi, Trypanosoma vivax, and Clostridioides difficile. If the discovery of irreversible inhibitors of T. cruzi PRAC (TcPRAC) led to innovative therapy of the Chagas disease, no inhibitors of CdPRAC have been discovered to date. However, C. difficile, due to an increased incidence in recent years, is considered as a major cause of health threat. In this work, we have taken into account the similarity between TcPRAC and CdPRAC enzymes to design new inhibitors of CdPRAC. Starting from (E) 4-oxopent-2-enoic acid TcPRAC irreversible inhibitors, we synthesized 4-aryl substituted analogs and evaluated their CdPRAC enzymatic inhibition against eleven strains of C. difficile. This study resulted in promising candidates and allowed for identification of (E)-4-(3-bromothiophen-2-yl)-4-oxobut-2-enoic acid 20 that was chosen for complementary in vivo studies and did not reveal in vivo toxicity.
Published: 2021

13. Induction of Human Trophoblast Stem Cells from Somatic Cells and Pluripotent Stem Cells

Author: Castel, Gaël, Meistermann, Dimitri, Bretin, Betty, Firmin, Julie, Blin, Justine, Loubersac, Sophie, Bruneau, Alexandre, Chevolleau, Simon, Kilens, Stéphanie, Chariau, Caroline, Gaignerie, Anne, Francheteau, Quentin, Kagawa, Harunobu, Charpentier, Eric, Flippe, Léa, François--Campion, Valentin, Haider, Sandra, Dietrich, Bianca, Knöfler, Martin, Arima, Takahiro, Bourdon, Jérémie, Rivron, Nicolas, Masson, Damien, Fournier, Thierry, Okae, Hiroaki, Fréour, Thomas, David, Laurent, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CCSD, Accord Elsevier, Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire des Sciences du Numérique de Nantes (LS2N), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Structure fédérative de recherche François Bonamy (SFR François Bonamy), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), Austrian Academy of Sciences (OeAW), Medizinische Universität Wien = Medical University of Vienna, Tohoku University [Sendai], and The Enteric Nervous System in gut and brain disorders [U1235] (TENS)
Subjects: Pluripotent Stem Cells, human induced trophoblast stem cells, induced pluripotent stem cells, [SDV]Life Sciences [q-bio], naive pluripotent stem cells, Cell Differentiation, somatic cell reprogramming, Trophoblasts, cell fate conversion, [SDV] Life Sciences [q-bio], human placenta, Pregnancy, embryonic structures, Humans, OSKM, Female, extended pluripotent stem cells, trophoblast stem cells, human peri-implantation embryo, reproductive and urinary physiology
Abstract: International audience; Human trophoblast stem cells (hTSCs) derived from blastocysts and first-trimester cytotrophoblasts offer an unprecedented opportunity to study the placenta. However, access to human embryos and first-trimester placentas is limited, thus preventing the establishment of hTSCs from diverse genetic backgrounds associated with placental disorders. Here, we show that hTSCs can be generated from numerous genetic backgrounds using post-natal cells via two alternative methods: (1) somatic cell reprogramming of adult fibroblasts with OCT4, SOX2, KLF4, MYC (OSKM) and (2) cell fate conversion of naive and extended pluripotent stem cells. The resulting induced/converted hTSCs recapitulated hallmarks of hTSCs including long-term self-renewal, expression of specific transcription factors, transcriptomic signature, and the potential to differentiate into syncytiotrophoblast and extravillous trophoblast cells. We also clarified the developmental stage of hTSCs and show that these cells resemble day 8 cytotrophoblasts. Altogether, hTSC lines of diverse genetic origins open the possibility to model both placental development and diseases in a dish.
Published: 2020

14. Assessment of Neonatal Intensive Care Unit Practices and Preterm Newborn Gut Microbiota and 2-Year Neurodevelopmental Outcomes

Author: Marie-José Butel, Pierre-Yves Ancel, Josef Neu, Julio Aires, Karine Le Roux, Jean-Christophe Rozé, Clotilde Rousseau, Emmanuel Montassier, Matthieu Resche-Rigon, Céline Monot, Patricia Lepage, Marine Butin, Laetitia Marchand-Martin, Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL), PremUp Foundation, Institut de Recherche pour le Développement (IRD)-CHI Créteil-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP), University of Central Florida [Orlando] (UCF), ANR-12-BSV3-0025,EPIFLORE,Ecosystème intestinal du grand et très grand prématuré: analyse du microbiote, implications cliniques à court et long term(2012), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut de Recherche pour le Développement (IRD)-CHI Créteil-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris-Saclay-Université Paris Cité (UPCité)
Subjects: Male, Pediatrics, medicine.medical_specialty, Neonatal intensive care unit, [SDV]Life Sciences [q-bio], Population, INFANTS, Infant, Premature, Diseases, 03 medical and health sciences, NECROTIZING ENTEROCOLITIS, 0302 clinical medicine, Intensive Care Units, Neonatal, Intensive care, Humans, Medicine, Prospective Studies, education, Original Investigation, 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, Research, Confounding, Infant, Newborn, Infant, Gestational age, General Medicine, Odds ratio, Gastrointestinal Microbiome, 3. Good health, Online Only, Neurodevelopmental Disorders, Child, Preschool, Infant, Extremely Premature, Infant Care, Cohort, Dysbiosis, Female, business, 030217 neurology & neurosurgery, Cohort study
Abstract: Key Points Question What are the long-term outcomes associated with dysbiosis of gut microbiota in very preterm newborns? Findings In this cohort study of 577 very preterm newborns across 24 neonatal intensive care units from a French nationwide cohort, gut microbiota at week 4 after birth showed 6 bacterial patterns that varied according to gestational age, perinatal characteristics, individual treatments, and neonatal intensive care unit strategies. Three clusters were associated with 2-year outcomes after adjustment for these confounders. Meaning Modifying strategies associated with alterations in microbiota, such as promoting enteral nutrition, reducing sedation use, promoting early extubation, or skin-to-skin practice, may be correlated with outcomes in preterm newborns., Importance In very preterm newborns, gut microbiota is highly variable with major dysbiosis. Its association with short-term health is widely studied, but the association with long-term outcomes remains unknown. Objective To investigate in preterm newborns the associations among practice strategies in neonatal intensive care units (NICUs), gut microbiota, and outcomes at 2 years. Design, Setting, and Participants EPIFLORE is a prospective observational cohort study that includes a stool sample collection during the fourth week after birth. Preterm newborns of less than 32 weeks of gestational age (GA) born in 2011 were included from 24 NICUs as part of the French nationwide population-based cohort, EPIPAGE 2. Data were collected from May 2011 to December 2011 and analyzed from September 2016 to December 2018. Exposures Eight NICU strategies concerning sedation, ventilation, skin-to-skin practice, antibiotherapy, ductus arteriosus, and breastfeeding were assessed. A NICU was considered favorable to a practice if the percentage of that practice in the NICU was more than the expected percentage. Main Outcomes and Measures Gut microbiota was analyzed by 16S ribosomal RNA gene sequencing and characterized by a clustering-based method. The 2-year outcome was defined by death or neurodevelopmental delay using a Global Ages and Stages questionnaire score. Results Of 577 newborns included in the study, the mean (SD) GA was 28.3 (2.0) weeks, and 303 (52.5%) were male. Collected gut microbiota was grouped into 5 discrete clusters. A sixth cluster included nonamplifiable samples owing to low bacterial load. Cluster 4 (driven by Enterococcus [n = 63]), cluster 5 (driven by Staphylococcus [n = 52]), and cluster 6 (n = 93) were significantly associated with lower mean (SD) GA (26.7 [1.8] weeks and 26.8 [1.9] weeks, respectively) and cluster 3 (driven by Escherichia/Shigella [n = 61]) with higher mean (SD) GA (29.4 [1.6] weeks; P = .001). Cluster 3 was considered the reference. After adjustment for confounders, no assisted ventilation at day 1 was associated with a decreased risk of belonging to cluster 5 or cluster 6 (adjusted odds ratio [AOR], 0.21 [95% CI, 0.06-0.78] and 0.19 [95% CI, 0.06-0.62], respectively) when sedation (AOR, 10.55 [95% CI, 2.28-48.87] and 4.62 [1.32-16.18], respectively) and low volume of enteral nutrition (AOR, 10.48 [95% CI, 2.48-44.29] and 7.28 [95% CI, 2.03-26.18], respectively) was associated with an increased risk. Skin-to-skin practice was associated with a decreased risk of being in cluster 5 (AOR, 0.14 [95% CI, 0.04-0.48]). Moreover, clusters 4, 5, 6 were significantly associated with 2-year nonoptimal outcome (AOR, 6.17 [95% CI, 1.46-26.0]; AOR, 4.53 [95% CI, 1.02-20.1]; and AOR, 5.42 [95% CI, 1.36-21.6], respectively). Conclusions and Relevance Gut microbiota of very preterm newborns at week 4 is associated with NICU practices and 2-year outcomes. Microbiota could be a noninvasive biomarker of immaturity., This cohort study of 577 very preterm newborns across 24 neonatal intensive care units from a French nationwide cohort investigates associations among practice strategies, gut microbiota, and outcomes at 2 years.
Published: 2020

15. Anaerobe

Author: Nagham Khanafer, Alain Gravet, Philippe Vanhems, Benoit Guery, Frédéric Barbut, David Boutoille, Anaelle Hemmendinger, Anne Vachee, Anne Marie Rogues, Dominique Vanjak, Fondation Mérieux, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), ESCMID Study Group for Clostridioides Difficile (ESGCD), Université de Lausanne = University of Lausanne (UNIL), CHU Roubaix, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Groupe hospitalier de la région de Mulhouse et Sud-Alsace, Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Curie [Paris], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), and Astellas Pharma
Subjects: Point prevalence survey, Adult, Male, medicine.medical_specialty, genetic structures, Adolescent, Microbiology, European studies, 03 medical and health sciences, Young Adult, Risk Factors, Epidemiology, Prevalence, Medicine, Humans, Registries, 030304 developmental biology, Aged, Aged, 80 and over, 0303 health sciences, Surveillance, 030306 microbiology, business.industry, Mortality rate, Incidence (epidemiology), Incidence, Gender distribution, Middle Aged, 3. Good health, Europe, Infectious Diseases, Clostridioides difficile infection, Population Surveillance, Emergency medicine, Epidemiological surveillance, Clostridium Infections, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, France, Symptom Assessment, business, Clostridioides
Abstract: International audience; INTRODUCTION: The magnitude and scope of Clostridioides difficile infection (CDI) has changed with an increase in incidence and severity. The epidemiology of CDI is not well known in France due to difficulties to conduct large continuous surveillance. The objectives were to compare the characteristics of patients with CDI collected through repeated point prevalence survey via DIFTEC™, a free electronic tool, with those from previous French or European studies. METHODS: DIFTEC™ was developed to evaluate epidemiological burden, diagnostic strategies and management of CDI in France. National and European guidelines were used for definitions. A literature review of studies conducted in Western Europe on CDI and published between January, 2008 and May, 2018 was done to compare their data with those included in the DIFTEC™ database. RESULTS: From January 2016, to December 2017, 455 CDI episodes from 22 French hospitals were included. Most of CDI cases were health-care associated (HCA) (78%). The comparison between included patients and French literature data showed that the rates of previous antibiotics exposure, crude mortality and recurrence were not statistically different. However HCA-CDI was significantly more frequent in the DIFTEC™ study. Gender distribution, recurrence and crude mortality rates were not statistically different compared to European data. HCA-CDI was more frequent in the DIFTEC™ study whereas previous treatment with proton pump inhibitors and antibiotics were significantly higher in European studies. DISCUSSION: These results illustrated the added value of a new tool for increasing the reliable knowledge of CDI in France based on epidemiological surveillance implemented in health-care settings.
Published: 2020

16. Rilpivirine in HIV-1-positive women initiating pregnancy

Author: Frange, Pierre, Tubiana, Roland, Sibiude, Jeanne, Canestri, Ana, Arvieux, Cédric, Brunet-Cartier, Cécile, Cotte, Laurent, Reynes, Jacques, Mandelbrot, Laurent, Warszawski, Josiane, Le Chenadec, Jérôme, Crenn-Hebert, Catherine, Floch-Tudal, Corinne, Mazy, Fabienne, Joras, Marine, Meier, Françoise, Mortier, Emmanuel, Briquet, Catherine, Ichou, Houria, Marty, Laurence, Jabbarian, Hélène, Ceccaldi, Pierre-François, Villemant, Agnès, Zarouk, Virginie, Lefort, Agnès, Ben Salah, Mariam, Hittinger, Gilles, Chamouilli, Jean-Marc, Burle, Christian, Lafeuillade, Alain, Philip, Gisèle, Lambry, Véronique, Medus, Marie, Bachelard, Germaine, Malet, Martine, Dendale-Nguyen, Joëlle, Guimard, Thomas, Guimard, Karine, Brossier, Jean-Pierre, Perre, Philippe, Esnault, Jean-Luc, Aubry, Olivier, Leautez-Nainville, Sophie, Bonnenfant, Valerie, Laine, Laeticia, Martha, Sandrine-Anne, Maurel, Elise, Francoise, Michel, Barat, Muriel, Murger, Patricia, Rouha, Mahfoud, Lévy, Marc, Lumbroso, Philippe, Checoury, Alain, Sahadatu, Osseni, Perfezou, Pascale, Blondin, Gilles, Ansart, Séverine, De Saint Martin, Luc, Le Moine, Philippe, Duthé, Jean-Charles, Daniel, Corinne, Calvez, Christian, Boutaric, Emmanuelle, Rohan, Jennifer, Bauville, Estelle, Dupre, Christelle, Lotton, Pascal, Ouamara-digue, Enora, Poinsignon, Yves, Goussef, Marie, Grelier, Anne, Mousset, Gaetane, Cudeville, Corinne, Niault, Mathilde, Belzic, Isabelle, Moreau, Philippe, Le Coz, Marie-Françoise, Vaillant, Odile Luycx, Guerin-Duplessy, Anne, Mouton-Rioux, Virginie, De Morel, Philippe, Vitrat, Virginie, Tardif, Didier, Gaillat, Jacques, Vanderbergh, Anne, Braig, Suzanne, Clavere, Gaelle, Dehlinger-Paul, Marion, Mohamed, Khaled, Echard, Marie, Camus, Michel, Mulard, Catherine, Fontelonga, Marie-Agnès, Heller-Roussin, Brigitte, Winter, Cécile, Challier, Marion, Debruyne, Elise, Marcou, Valerie, Firtion, Ghislaine, Pannier, Emmanuelle, Costa, Myriam, Launay, Odile, Salmon-Ceron, Dominique, Belkacem, Touria, Bajawi, Youcef, Aubret, Valérie Raynal, Rivaux, Danièle, Elaoun, Neila, Allal, Lahcene, Djoubou, Sandrine, Rahli, Djamila, Moine, Agnès Bourgeois, Valentin, Morgane, Damond, Florence, Huri, Virginie, Vivier, Valérie, Yahia, Fatma Ait, Garrait, Valérie, Hau, Isabelle, Touboul, Claudine, Ratsimbazafy, Lanto, Boiron, Emilie, Elharrar, Brigitte, Labaune, Jean-Marc, Rudigoz, Rene-Charles, Brochier, Corinne, Galvan, Valérie, Ogoudjobi, Stanislas, Elleau, Christophe, Runel-Belliard, Camille, Pistone, Thierry, Fleury, Hervé, Horovitz, Jacques, Sandler, Boris, Roux, Denis, Ragnaud, Jean-Marie, Chabanier, Pierre, Brun, Jean-Luc, Delveaux, Sandrine, Muanza, Blandine, Diallo, Mama Doufari, Lamaury, Isabelle, Sow, Marie-Thérèse, Samar, Ketty, Carpentier, Bénédicte, Osman, Zafer, Dienga, Etienne, Seaume, Hervé, Ducrocq, Sarah, Bailly-Salin, Philippe, Da Silva, Christelle Dusart, Fayolas, Isabelle, Abbal, Julie, Simon-Toulza, Caroline, Truillet, Véronique, Bogner, Noëlle, Chiabrando, Julie, Armand, Evelyne, Cayla, Claudine, Chacé, Anne, Matheron, Isabelle, Richier, Laurent, Miantezila, Joe, Bry, Sandrine, Couderc, Sophie, Narcy, Catherine, Routier, Corinne, Nassar, Rania, Bouldouyre, Marie-Anne, Zakaria, Ahmed, Dauphin, Hélène, Goissen, Céline, Belloy, Marie, Delassus, Jean-Luc, Favret, Véronique, Nemeth, Céline, Partisani, Marialuisa, Entz-Werlé, Natacha, Langer, Bruno, Uettwiller, Françoise, Durand, Myriam, Partizani, MariaLuisa, Cheneau, Christine, Rey, David, Ebel, Edith, Fischer, Patricia, DAVID, Eric, Vayssière, Christophe, Weil, Michèle, Schmitt, Marie Paule, Nisand, Israël, Genet, Philippe, Brault, Dominique, Allisy, Christine, Gerbe, Juliette, Masse, Virginie, Wifaq, Bouchra, Courdavault, Laurence, Gabor, Petra, Tordjeman, Nathalie, Lebrette, Marie-Gisèle, Selleret, Lise, Samama, Déborah, Bolot, Pascal, Khuong-Josses, Marie-Aude, Amel, Mahdi, Bounan, Stéphane, Nourry, Christelle, Andris, Sabine, Blanche, Stephane, Driessen, Marine, Veber, Florence, Fischer, Alain, Rouzioux, Christine, Avettand-Fenoël, Véronique, Mahlaoui, Nizar, Mourey, Marie-Christine, Granier, Michèle, Devidas, Alain, Donnadieu, Anne-Claire, May, Adrien, Chabrol, Amélie, Chevojon, Pierre, Bellahcene, Chahrazede, Sanchez, Audrey, Malbrunot, Claire, Neizelien, Joelle, Agher, Nouara, Pluchart, Claire, Rouger, Christine, Dommergues, Marc, Bonmarchand, Manuela, Shneider, Luminata, Caby, Fabienne, Calin, Ruxandra-Oana, Blanc, Christine, Lupin, Catherine, Pauchard, Michèle, Yangui, Mohamed Amine, Roca, Didier, Todorova, Darina, Laurent, Juliette, Ferry, A., Deschaud, Martine, Blum, Laurent, Chambrin, Véronique, Labrune, Philippe, Clech, Laure, Raho-Moussa, Mariem, Pauly-Ravelly, Isolde, Jault, Thierry, Bouabdallah, Soufiane, Sanchez, Lydie, Sanchez, Anita, Johnson, Ama, Louchard, Agnès, Allouche, Claude, Pathe, Jean-Paul, Lachassine, Eric, Benoist, Laurence, Jeantils, Vincent, Delannoy, Catherine, Benbara, Amélie, Carbillon, Lionel, Borgne, Anne, Moreau, Laurence, PICARD, Fabienne, Karaoui, Leïla, Elbert, Véronique Lefevre, Balaz, Valérie, Bongain, André, Monpoux, Fabrice, Deville, Anne, Galiba, Eliane, Jabbar, Ahmed, Joutel, Martine, Schmidt, Jean-Luc, Decaux, Nathalie, Cravello, Ludovic, Errichiello, Katia, Hubert, Claire, Dollfus, Catherine, Hervé, François, Tabone, Marie-Dominique, Courcoux, Mary-France, Leverger, Guy, Kayem, Gilles, Schnurgier, Aurélie, Jensen, Aurore, Vaudre, Geneviève, Pinquier, Didier, Gromez, Alexis, Pinto-Cardoso, Gaelle, Faye, Albert, Borie, Constance, Levine, Martine, Matheron, Sophie, Marouts, Erianna Bellaton, Boissinot, Christine, Caseris, Marion, Pommelet, Virginie, Morau, Geneviève, Leveille, Sandrine, Boumediene, Marie Astride, Garion, Dominique, Peretti, Delphine, Fourcade, Corinne, Houllier, Marie, Jrad, Ikram, Bourdic, Katia, Monnier, Sylvie, Chirouze, Catherine, Proust, Aurélie, Catteau, Odile, Gardiennet, Quentin, Reliquet, Véronique, Winer, Norbert, Vaucel, Edouard, Rodallec, Audrey, Garnier-André, Elisabeth, Briandet, Claire, Brouard, Jacques, Goubin, Pascale, Beucher, Gaël, Dina, Julia, Demersay, Arnaud Chalvon, Tassi, Sylvie, Lavarenne, Gaelle, Rajguru, Mandovi, Messaoudi, Fabienne, Carré, Nathalie, Rajguru, Mandavi, Bobrie-Moyrand, Claire, Foucaud, Pierre, Bernard, Louis, Maakroun, Zoha, Bourgault, Olivier, Kebaili, Kamila, Bertrand, Yves, Alixe, Véronique, Boyer, Emeline, Billiemaz, Kareen, Fanget, Cécile, Ronat, Véronique, Lesauder, Catherine, Lavastre, Marie Laure, Moulin, Alice, Turquini, Marie-France, Colombani, Dominique, Belgodere, Danièle, Fialaire, Pascale, Proust, Stéphanie, Rehaiem, Sami, Mesnard, Louis, Werner, Evelyne, Dukiel, Nathalie, Desmergers, Baya, Blanc-Ruffat, Isabelle, Maraux, Barbara, Coursol, Anne, Castaneda, Julie, Etienne, Lise, Vintejoux, Emmanuelle, Lalande, Muriel, Segondy, Michel, Guigue, Nelly, De Gennes, Christiane, Clavel, Cyril, Cazassus, François, Walter, Véronique, Mazingue, Françoise, Hammou, Yamina, Lagree, Marion, Paquiez, Odile, D’angelo, Sophie, Boquet, Laurence, Ajana, Faiza, Hatchuel, Yves, Nahri, Imad, Zebelus, Jenny, Genet, Claire, Ducroix-Roubertou, Sophie, Aubrard, Yves, Constanty, Anne, Weinbreck, Pierre, Piet, Emilie, Jacquier, Françoise, Michaud, Christophe, Safwan, Hassan, Boutet, Arnaud, Grand-Courault, Carole, Autret, Fanny, Habibi, Fakher, Azria, Elie, Abdelhadi, Mohamed, Elenga, Narcisse, Bocket, Laurence, Taillet, Françoise, Palenzuela, Gilles, Khadly, Redouane, Pierronnet, Danielle, Dos-Santos, Emmanuelle, David, Selva, Makhloufi, Djamila, Brunel-Dalmas, Florence, Carbonnel-Delalande, Elisabeth, Chiarello, Pierre, Godinot, Matthieu, Gilbert, Sylvie, Massardier, Jérôme, Gauthier-Moulinier, Hélène, Fernandes, Elisabeth, Ranaivojaona, Sata, Chevry, Coralie, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département de maladies infectieuses, Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Louis Mourier - AP-HP [Colombes], Chirurgie Gynécologique et Obstétrique (CGO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'infectiologie [AP-HP Hôpital Louis Mourier, Colombes], Faculté de Médecine Paris-Diderot [Paris], Université Paris Diderot - Paris 7 (UPD7), Service de Médecine Interne [AP-HP, CHU Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Service de médecine interne, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Service de pédiatrie, Centre Hospitalier Chalon-sur-Saône William Morey, CH de Lorient, Laboratoire de Traitement de l'Information Medicale (LaTIM), Université européenne de Bretagne - European University of Brittany (UEB)-Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Unité d'hémato-oncologie, CHU Toulouse [Toulouse], Pôle Médico-Chirurgical de Pédiatrie et de Génétique Clinique, Néonatologie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CH Bretagne Sud, Centre d'Investigations Biomédicales - Hématologie - Oncologie - Greffes (CIB-HOG), Centre d'Investigations Biomédicales - Hématologie - Oncologie - Greffes-Hopital St Louis, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Service des Maladies Infectieuses, Centre Hospitalier de la Région d'Annecy (Pringy), University of Warwick [Coventry], Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital de la Croix-Rousse [CHU - HCL], Réseau périnatal Aurore, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Bordeaux [Bordeaux], pôle gynécologie-obstétrique et médecine foetale, Laboratoire Rhéologie et Procédés (LRP), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Fédération des Maladies Infectieuses [Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Centre de compétences des microangiopathies thrombotiques, department of pathology, university hospital, parakou, CHU Pointe-à-Pitre/Abymes [Guadeloupe], Service des Maladies Infectieuses et Tropicales[Point-à-Pitre], Service de Gynécologie-Obstétrique [Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Strasbourg, Développement et physiopathologie de l'intestin et du pancréas, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de gynécologie–obstétrique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], CHRU Strasbourg, Département d'échographie et de Médecine fœtale, SIHCUS-CMCO, Service de Gynécologie-Obstétrique, CHI Poissy-Saint-Germain, Centre Hospitalier Victor Dupouy, Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hôpital d'Argenteuil, Centre Hospitalier de Saint-Denis [Ile-de-France], Hôpital Delafontaine, Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants (UMR_S 953), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de microbilogie & unité d'immunologie, hématologie et rhumatologie pédiatriques, Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), Laboratoire de Virologie [CHU Necker], Université Sorbonne Paris Cité (USPC), IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Médecine néonatale, Centre Hospitalier Sud Francilien, Service de pneumologie [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Gynécologie-Obstétrique, Maternité, Chirurgie Gynécologique [CHU Pitié-Salpêtrière], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Référence Maladies Héréditaires du Métabolisme Hépatique [Hôpital Antoine Béclère - APHP (CRMR), Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Service de gynécologie-obstétrique [Hôpital Jean Verdier], Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], Service de Gynécologie-Obstétrique-Reproduction, Hôpital l'Archet, Service d'Hémato-oncologie Pédiatrique [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Trousseau [APHP], Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Service des maladies infectieuses et tropicales, Service de pédiatrie générale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Institut Pasteur du Laos, Réseau International des Instituts Pasteur (RIIP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Gynécologie Obstétrique, Service de Médecine Interne et Immunologie clinique [AP-HP Hôpital Bicêtre], Hôpital Bicêtre, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), service de maladies infectieuses CHU J Minjoz Besancon, Service des maladies infectieuses et tropicales [CHU Nantes], Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de virologie [CHU Nantes], Service de Pédiatrie Enfants - Hématologie Oncologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Pédiatrie Médicale [Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Gynécologie-Obstétrique et Médecine de la Reproduction [CHU Caen], Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Médecine Interne et Maladies Infectieuses [Tours], Service d'hématologie : Immuno-Hématologie pédiatrique et transplantation de moelle osseuse, Hôpital Debrousse, CHU Saint-Etienne, Centre population et développement (CEPED - UMR_D 196), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Médecine Néonatale et Réanimation Pédiatrique, CH René Dubos, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service des Maladies Infectieuses et Tropicales [Hôpital Gustave Dron, Tourcoing], Centre Hospitalier Gustave Dron [Tourcoing], 'Personal Protection Against Vectors' working group (PPAV), PPAV working group, Service des Maladies infectieuses et tropicales [CHU Limoges], CHU Limoges, Equipe de Recherche Médicale Appliquée (ERMA), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), CHU Annecy, Service de Pédiatrie, Centre hospitalier de Saint-Nazaire, EA 3593 Université des Antilles et de la Guyane, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Laboratoire de virologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Service d'immunologie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Centre Hospitalier de Basse-Terre, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Université de Rennes (UR), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Collège de France - Chaire Médecine expérimentale (A. Fischer), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), ANRS CO1/CO11, French national, Viral Hepatitis, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service des maladies infectieuses et tropicales [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Mines-Télécom [Paris] (IMT), Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11), CH Evry-Corbeil-CH Evry-Corbeil, CH Evry-Corbeil, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13), Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Laboratoire d'Electrotechnique de Lyon (LEL), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon, Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM)
Subjects: rilpivirine, viral suppression, hiv, hiv-1, pregnancy, conception, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, virology
Abstract: International audience; BackgroundSafety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasma concentrations are reduced during second/third trimesters, with a potential risk of viral breakthroughs. Thus, French guidelines recommend switching to rilpivirine-free combinations (RFCs) during pregnancy.ObjectivesTo describe the characteristics of women initiating pregnancy while on rilpivirine and to compare the outcomes for virologically suppressed subjects continuing rilpivirine until delivery versus switching to an RFC.MethodsIn the ANRS-EPF French Perinatal cohort, we included women on rilpivirine at conception in 2010–18. Pregnancy outcomes were compared between patients continuing versus interrupting rilpivirine. In women with documented viral suppression (
Published: 2020

17. Comparative Study of PPARγ Targets in Human Extravillous and Villous Cytotrophoblasts

Author: Mickael Guesnon, Wencan Zhu, Séverine A. Degrelle, Karine Clément, Thierry Fournier, Christine Rouault, Fulin Liu, Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), PremUp Foundation, Institut de Recherche pour le Développement (IRD)-CHI Créteil-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris-Saclay-Université Paris Cité (UPCité), MIA, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Inovarion, and PELLOUX-GERVAIS, Véronique
Subjects: 0301 basic medicine, 030219 obstetrics & reproductive medicine, Article Subject, Microarray analysis techniques, QH301-705.5, Cellular differentiation, [SDV]Life Sciences [q-bio], Placentation, Promoter, Biology, Cell biology, Transcriptome, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Drug Discovery, Pharmacology (medical), Cytotrophoblasts, KEGG, Biology (General), Gene, Research Article
Abstract: Trophoblasts, as the cells that make up the main part of the placenta, undergo cell differentiation processes such as invasion, migration, and fusion. Abnormalities in these processes can lead to a series of gestational diseases whose underlying mechanisms are still unclear. One protein that has proven to be essential in placentation is the peroxisome proliferator-activated receptor γ (PPARγ), which is expressed in the nuclei of extravillous cytotrophoblasts (EVCTs) in the first trimester and villous cytotrophoblasts (VCTs) throughout pregnancy. Here, we aimed to explore the genome-wide effects of PPARγ on EVCTs and VCTs via treatment with the PPARγ-agonist rosiglitazone. EVCTs and VCTs were purified from human chorionic villi, cultured in vitro, and treated with rosiglitazone. The transcriptomes of both types of cells were then quantified using microarray profiling. Differentially expressed genes (DEGs) were filtered and submitted for gene ontology (GO) annotation and pathway analysis with ClueGO. The online tool STRING was used to predict PPARγ and DEG protein interactions, while iRegulon was used to predict the binding sites for PPARγ and DEG promoters. GO and pathway terms were compared between EVCTs and VCTs with clusterProfiler. Visualizations were prepared in Cytoscape. From our microarray data, 139 DEGs were detected in rosiglitazone-treated EVCTs (RT-EVCTs) and 197 DEGs in rosiglitazone-treated VCTs (RT-VCTs). Downstream annotation analysis revealed the similarities and differences between RT-EVCTs and RT-VCTs with respect to the biological processes, molecular functions, cellular components, and KEGG pathways affected by the treatment, as well as predicted binding sites for both protein-protein interactions and transcription factor-target gene interactions. These results provide a broad perspective of PPARγ-activated processes in trophoblasts; further analysis of the transcriptomic signatures of RT-EVCTs and RT-VCTs should open new avenues for future research and contribute to the discovery of possible drug-targeted genes or pathways in the human placenta.
Published: 2020

18. Placental production of progestins is fully effective in villous cytotrophoblasts and increases with the syncytiotrophoblast formation

Author: Ioana Ferecatu, Marylise Hebert-Schuster, Anthony Garnier, P. Gerbaud, Thierry Fournier, A. Bouzerara, Séverine Trabado, Isabelle Hernandez, Camille Fraichard, F. Bonnet, Jean Guibourdenche, Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de génétique moléculaire, pharmacogénétique et hormonologie, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, Placenta, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, Steroid Isomerases, Biochemistry, Gas Chromatography-Mass Spectrometry, Andrology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Syncytiotrophoblast, Multienzyme Complexes, Pregnancy, medicine, Humans, Molecular Biology, reproductive and urinary physiology, Cells, Cultured, Progesterone, Cell Proliferation, Forskolin, Cytotrophoblast, TNF Receptor-Associated Factor 4, Progesterone Reductase, Cholesterol side-chain cleavage enzyme, 17-alpha-Hydroxyprogesterone, Colforsin, Trophoblast, Cell Differentiation, Trophoblasts, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, chemistry, Gene Expression Regulation, Pregnenolone, HSD3B1, Female, Cytotrophoblasts, Progestins, medicine.drug
Abstract: Placental syncytiotrophoblast (ST) is considered as the main placental endocrine tissue secreting progesterone, a steroid essential for maintenance of pregnancy. However, each step of progestins production has been poorly investigated in villous cytotrophoblast (VCT) regarding ST formation. We aimed to characterize progestins production during human differentiation of VCT into ST. VCTs were isolated from term placenta and cultivated, with or without forskolin (FSK), to stimulate trophoblast differentiation. Secreted progestins concentrations were determined by immuno-assay and Gas Chromatography-tandem mass spectrometry. Intracellular expression of cholesterol transporter and enzymes involved in steroidogenesis were studied by immunofluorescence, western-blot, and RT-qPCR. Progesterone and pregnenolone are produced by VCT and their secretion increases with VCT differentiation while 17-hydroxyprogesterone concentration remains undetectable. HSD3B1 enzyme expression increases whereas MLN64, the cholesterol placental mitochondrial transporter and P450SCC expressions do not. FSK induces progestins production. Progestins placental synthesis is effective since VCT and increases with ST formation thanks to mitochondria.
Published: 2020

19. Assessment of dually labelled PEGylated liposomes transplacental passage and placental penetration using a combination of two ex-vivo human models: the dually perfused placenta and the suspended villous explants

Author: Sophie Gil, Christelle Simasotchi, Karine Andrieux, Khair Alhareth, Thierry Fournier, Lucie Valero, Nathalie Mignet, Daniel Scherman, Caroline Roques, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de pharmacologie chimique et génétique et d'imagerie (UPCGI - UMR 8151 / UMR_S 1022 ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)
Subjects: 0301 basic medicine, Placenta, Pharmaceutical Science, Biology, Polyethylene Glycols, Andrology, 03 medical and health sciences, 0302 clinical medicine, Syncytiotrophoblast, Pregnancy, medicine, Humans, Maternal-Fetal Exchange, ComputingMilieux_MISCELLANEOUS, Fluorescent Dyes, Liposome, 030219 obstetrics & reproductive medicine, Rhodamines, Phosphatidylethanolamines, Transplacental, Penetration (firestop), Fluoresceins, Virology, 3. Good health, Perfusion, Drug Liberation, [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, 030104 developmental biology, Fetal circulation, medicine.anatomical_structure, Liposomes, embryonic structures, Female, Nanocarriers, Ex vivo
Abstract: Uptake and passage of nanocarriers through the placenta are critical information to develop new therapeutic approaches during pregnancy. In order to assess nanocarriers transplacental passage and penetration into the placenta, we studied and optimized two ex-vivo human models: the dually perfused placenta and the placenta explants. Doubly labelled PEGylated liposomes were used as models to provide data on the penetration and transplacental passage of drugs and liposomes. A HPLC method was set-up to quantify both carboxyfluorescein and lipid-rhodamine. Transplacental passage was then quantified using HPLC and placental penetration was assessed using spinning disk microscopy. We found a similar transplacental passage rate for both free and encapsulated carboxyfluorescein as well as a homogeneous fluorescence intensity in the outer cell layer of the placental villous, the syncytiotrophoblast, and the mesenchyma. Besides, liposome-rhodamine was not detected in the fetal circulation. The absence of transplacental passage of PEGylated liposomes is also supported by their detection in the sole syncytiotrophoblast. The combination of two ex-vivo models and the monitoring of both the drug and the carrier provided consistent and complementary information. Overall, we suggest combining the perfused human placenta and the human explants villous models to evaluate nanocarriers designed for treatments during pregnancy.
Published: 2017

20. Virulence of new variant strains of Clostridium difficile producing only toxin A or binary toxin in the hamster model

Author: Claire Janoir, Jean-Christophe Marvaud, Catherine Eckert, Sergio Quevedo-Torres, Frédéric Barbut, Bactéries, Pathogènes et Santé (UBaPS), Faculté de Pharmacie, Université Paris-Sud - Paris 11 (UP11)-Université Paris-Sud - Paris 11 (UP11), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], 030106 microbiology, Hamster, Virulence, Clostridium difficile toxin A, Clostridium difficile toxin B, Biology, medicine.disease_cause, Microbiology, CDT, lcsh:Infectious and parasitic diseases, Pathogenesis, 03 medical and health sciences, medicine, lcsh:RC109-216, tcdA, tcdB, Pore-forming toxin, Toxin, Clostridium difficile, hamster, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Infectious Diseases, Original Article
Abstract: Pathogenesis of Clostridium difficile has been linked to production of toxins, including the large toxins A and B as well as the binary toxin CDT. Until recently, toxin A was only found in combination in clinical strains with the toxin B, unlike toxin B or CDT, which were found alone in toxigenic variants. New toxigenic variants of C. difficile detected in our laboratory from patients with diarrhoea or severe colitis, including a variant producing only toxin A, were tested for virulence in the hamster model, which displays the clinical features of C. difficile disease. Hamsters infected with a strain producing only toxin B induced similar clinical signs, time to death from infection and histologic damage compared to the hypervirulent strain 027. No mortality or clinical signs of infection but caecal histologic damage was found with the variant producing only toxin A. The C. difficile variant strain producing only CDT was able to kill one hamster out of seven; nevertheless, the surviving animals had few alteration of the caecum. Keywords: Clostridium difficile, tcdA, tcdB, CDT, hamster
Published: 2019

21. Variation of fetuin-A in maternal and fetal serum during human parturition

Author: Pierre Bedossa, Dominique Luton, Miguel Albuquerque, Pierre-François Ceccaldi, Julie Le Faouder, Jean Guibourdenche, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and CCSD, Accord Elsevier
Subjects: Adult, Male, Proteomics, alpha-2-HS-Glycoprotein, Pregnancy Trimester, Third, [SDV]Life Sciences [q-bio], Mothers, Physiology, Gestational Age, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, medicine, Humans, Longitudinal Studies, Prospective cohort study, Fetus, 030219 obstetrics & reproductive medicine, business.industry, Organ dysfunction, Parturition, Obstetrics and Gynecology, Fetal Blood, medicine.disease, Blood proteins, Fetuin, 3. Good health, [SDV] Life Sciences [q-bio], Reproductive Medicine, 030220 oncology & carcinogenesis, Cord blood, Female, Metabolic syndrome, medicine.symptom, business, Biomarkers, Maternal Serum Screening Tests
Abstract: Background parturition involves multiple signalling pathways and most advances in research underline the importance of fetal development and maturation in the timing of labour, especially the fetal pituitary-adrenal axis. But, there is currently no consensual hypothesis on all the physiological processes responsible for human parturition. Methods sixty low-risk pregnant women were enrolled in a prospective cohort. Maternal blood was sampled regularly during consultations each week in last trimester, at delivery and at postnatal consultation. Cord blood was collected at delivery. We used proteomic analysis to identify maternal blood biomarkers of potential interest, focusing on serum proteins from 39 W G in pregnancies to delivery and postpartum. Results among 56 peaks we identified variation in the N-terminal part of fetuin-A in maternal serum. Fetuin-A is a natural antagonist of TGF-beta and is able to bind calcium. We found a significant decrease in maternal serum fetuin-A in the days preceding delivery, independently of the mode of delivery. Also, there does not appear to be significant influence of the different fetal parameters (sex, Z-score) on maternal serum variations at delivery. Conclusion fetuin-A is described by the literature as a potential biomarker for organ dysfunction and metabolic syndrome disorders. The protein mineral homeostasis would be an interesting pathway to explore during pregnancy and particularly parturition.
Published: 2019

22. VEGF (Vascular Endothelial Growth Factor) Functionalized Magnetic Beads in a Microfluidic Device to Improve the Angiogenic Balance in Preeclampsia

Author: Marylise Hebert-Schuster, Edouard Lecarpentier, Kelly Pons, Laurence Lecomte-Raclet, Stéphanie Descroix, Jean Guibourdenche, Lucile Alexandre, Laura Trapiella-Alfonso, Simon Dumas, Lucie Huart, Laurent Malaquin, Camille Fraichard, Isabelle Broutin, Thierry Fournier, Jean-François Gaucher, Michel Vidal, Nathalie Gagey-Eilstein, Vassilis Tsatsaris, Laboratoire de Physique et d'Etude des Matériaux (UMR 8213) (LPEM), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Physico-Chimie-Curie (PCC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Nanosciences et Innovation pour les Matériaux, la Biomédecine et l'Energie (ex SIS2M) (NIMBE UMR 3685), Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et pharmacotoxicologie placentaire humaine : Microbiote pré & post natal (3PHM - UMR-S 1139), Équipe Ingénierie pour les sciences du vivant (LAAS-ELIA), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT), Chimie Organique, Médicinale et Extractive et Toxicologie Expérimentale (COMETE - UMR 8638), Laboratoire Physico-Chimie Curie [Institut Curie] (PCC), Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre-Gilles de Gennes pour la Microfluidique, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHI Créteil, Cibles Thérapeutiques et conception de médicaments (CiTCoM - UMR 8038), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CIC - Mère Enfant Necker Cochin Paris Centre (CIC 1419), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Hôtel-Dieu [Paris], Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse Capitole (UT Capitole), Descroix, Stephanie, Laboratoire de Physique et d'Etude des Matériaux (LPEM), Centre National de la Recherche Scientifique (CNRS)-ESPCI ParisTech-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Institut National Polytechnique (Toulouse) (Toulouse INP), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Equipe C-TAC (UMR 8638), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Hopital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de biochimie-hormonologie, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Placental growth factor, Vascular Endothelial Growth Factor A, Endothelium, endothelium, placenta, [SDV]Life Sciences [q-bio], Endogeny, Pilot Projects, morbidity, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 030204 cardiovascular system & hematology, Pharmacology, In Vitro Techniques, Sensitivity and Specificity, Preeclampsia, preeclampsia, 03 medical and health sciences, chemistry.chemical_compound, Magnetics, 0302 clinical medicine, Pre-Eclampsia, Placenta, Lab-On-A-Chip Devices, Internal Medicine, medicine, Humans, Endothelial dysfunction, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Vascular Endothelial Growth Factor Receptor-1, Chemistry, medicine.disease, 3. Good health, Trophoblasts, Vascular endothelial growth factor, [SDV] Life Sciences [q-bio], Apheresis, medicine.anatomical_structure, 030220 oncology & carcinogenesis, embryonic structures, Blood Component Removal, Angiogenesis Inducing Agents, Female, pregnancy, Blood Flow Velocity
Abstract: International audience; Preeclampsia is a hypertensive pregnancy disease associated with a massive increase in sFlt-1 (soluble form of the vascular endothelial growth factor 1) in the maternal circulation, responsible for angiogenic imbalance and endothelial dysfunction. Pilot studies suggest that extracorporeal apheresis may reduce circulating sFlt-1 and prolong pregnancy. Nonspecific apheresis systems have potential adverse effects because of the capture of many other molecules. Our concept is based on a specific and competitive apheresis approach using VEGF (vascular endothelial growth factor) functionalized magnetic beads to capture sFlt-1 while releasing endogenous PlGF (placental growth factor) to restore a physiological angiogenic balance. Magnetic beads were functionalized with VEGF to capture sFlt-1. Experiments were performed using PBS, conditioned media from human trophoblastic cells, and human plasma. The proof of concept was validated in dynamic conditions in a microfluidic device as an approach mimicking real apheresis. Magnetic beads were functionalized with VEGF and characterized to evaluate their surface ligand density and recognition capabilities. VEGF-coated magnetic beads proved to be an efficient support in capturing sFlt-1 and releasing PlGF. In static conditions, sFlt-1 concentration decreased by 33±13%, whereas PlGF concentration increased by 27±10%. In dynamic conditions, the performances were improved, with 40% reduction of sFlt-1 and up to 2-fold increase of free PlGF. The sFlt-1/PlGF ratio was reduced by 63% in the plasma of preeclamptic patients. Apheresis was also associated with VEGF release. A ligand-based approach using VEGF-coated beads is an effective approach to the capture of sFlt-1 and the release of endogenous PlGF. It offers new perspectives for the treatment of preeclampsia.
Published: 2019

23. Study of Human T21 Placenta Suggests a Potential Role of Mesenchymal Spondin-2 in Placental Vascular Development

Author: Benoît Sarazin, Josette Badet, Danièle Evain-Brion, Fabien Guimiot, Padma Murthi, Pascale Gerbaud, Jean Guibourdenche, Guillaume Pidoux, Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Signalisation et physiopathologie cardiovasculaire (UMRS1180), Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Obstetrics and Gynaecology [Melbourne], Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne-Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, University of Melbourne, Monash University [Clayton], Hudson Institute of Medical Research [Clayton], Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fondation PremUp, CHU Robert Debré, Proteomic Solutions [Saint-Marcel], and Pidoux, Guillaume
Subjects: 0301 basic medicine, medicine.medical_specialty, Angiogenesis, Placenta, Neovascularization, Physiologic, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Extracellular matrix, 03 medical and health sciences, Paracrine signalling, 0302 clinical medicine, Endocrinology, Pregnancy, Internal medicine, medicine, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, Fetus, Extracellular Matrix Proteins, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Mesenchymal stem cell, Placentation, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Cell biology, Endostatins, Neoplasm Proteins, Crosstalk (biology), [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Case-Control Studies, Intercellular Signaling Peptides and Proteins, Female, Down Syndrome, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Placental development is particularly altered in trisomy of chromosome 21 (T21)–affected pregnancies. We previously described in T21-affected placentae an abnormal paracrine crosstalk between the villus mesenchymal core and villus trophoblasts. T21-affected placentae are known to be characterized by their hypovascularity. However, the causes of this anomaly remain not fully elucidated. Therefore, the hypothesis of an abnormal paracrine crosstalk between fetal mesenchymal core and placental endothelial cells (PLECs) was evocated. Villus mesenchymal cells from control (CMCs) and T21 placentae (T21MCs) were isolated and grown in culture to allow their characterization and collection of conditioned media for functional analyses (CMC-CM and T21MC-CM, respectively). Interestingly, PLEC proliferation and branching ability were less stimulated by T21MC-CM than by CMC-CM. Protein array analysis identified secreted proangiogenic growth factors in CMC-CM, which were reduced in T21MC-CM. Combined mass spectrometry and biochemical analysis identified spondin-2 as a factor decreased in T21MC-CM compared with CMC-CM. We found that exogenous spondin-2 stimulated PLEC proliferation and established that T21MC-CM supplemented with spondin-2 recovered conditioned media ability to induce PLEC proliferation and angiogenesis. Hence, this study demonstrates a crosstalk between villus mesenchymal and fetal endothelial cells, in which spondin-2 secreted from mesenchymal cells plays a central role in placental vascular functions. Furthermore, our results also suggest that a reduction in spondin-2 secretion may contribute to the pathogenesis of T21 placental hypovascularity.
Published: 2019

24. Toxigenic Clostridium difficile carriage in general practice: results of a laboratory-based cohort study

Author: Valérie Lalande, Jeanne Couturier, S. Bouée, L. Grandvoinnet, Catherine Eckert, N. Day, A. Youssouf, Frédéric Barbut, CCSD, Accord Elsevier, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpitaux Universitaires de l'Est Parisien [Paris] (HUEP), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoires Centre Biologique Chemin Vert [Paris] (CBCV), Cemka-eval [Bourg La Reine], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Centre d'Immunologie et de Maladies Infectieuses (CIMI)
Subjects: 0301 basic medicine, Male, Community, Ribotyping, Feces, 0302 clinical medicine, Toxins, 030212 general & internal medicine, Prospective Studies, Child, ADP Ribose Transferases, Aged, 80 and over, Incidence (epidemiology), Incidence, General Medicine, Clostridium difficile, Middle Aged, Antimicrobial, Diarrhoea, 3. Good health, Community-Acquired Infections, Infectious Diseases, Child, Preschool, General practice, Carrier State, Female, Cohort study, Microbiology (medical), Adult, medicine.medical_specialty, Paris, Adolescent, 030106 microbiology, 03 medical and health sciences, Young Adult, Bacterial Proteins, Internal medicine, medicine, Humans, Aged, business.industry, Clostridioides difficile, Glutamate dehydrogenase, Infant, Newborn, Infant, Pcr ribotyping, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Carriage, Clostridium Infections, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business
Abstract: International audience; Objectives: Reported rates of community-acquired Clostridium difficile infections (CDIs) have been increasing. However, the true burden of the disease in general practice is unknown in France. Our objective was to determine the incidence of toxigenic C. difficile carriage and the percentage of stool samples prescribed by general practitioners (GPs) which contained free C. difficile toxins.Methods: During an 11-month period, all stool samples submitted for any enteric pathogen detection to 15 different private laboratories in Paris and the surrounding areas were tested for C. difficile, irrespective of the GPs' request. A clinical questionnaire was completed for each patient. Stool samples were screened using a rapid simultaneous glutamate dehydrogenase and toxins A/B detection test: any positive result (glutamate dehydrogenase or toxin) was further confirmed by the stool cytotoxicity assay (CTA) on MRC-5 cells and by toxigenic culture (TC) at a central laboratory. The C. difficile isolates were characterized by PCR ribotyping.Results: A total of 2541 patients (1295 female, 1246 male) were included. The incidences of patients with a positive toxigenic culture and a positive CTA were 3.27% (95% CI 2.61%-4.03%) and 1.81% (95% CI 1.33%-2.41%), respectively. GPs requested C. difficile testing in only 12.93% of the stool samples, detecting 52.30% of all TC-positive patients. The 83 toxigenic C. difficile strains belonged to 36 different PCR ribotypes.Conclusions: Toxigenic C. difficile carriage is frequent in general practice but remains under-recognized. It may affect young patients without previous antimicrobial therapy or hospitalization.
Published: 2019

25. Expression, Localization, and Activity of the Aryl Hydrocarbon Receptor in the Human Placenta

Author: Ioana Ferecatu, Xavier Coumoul, Margaux Nedder, Francoise Vibert, Jessica Dalmasso, Thierry Fournier, Céline Tomkiewicz-Raulet, Sophie Gil, Audrey Chissey, Anaïs Wakx, Sonja Boland, Séverine A. Degrelle, Benoist, David, Chimie Organique, Médicinale et Extractive et Toxicologie Expérimentale (COMETE - UMR 8638), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), and Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, CYP1A1, Gene Expression, lcsh:Chemistry, 0302 clinical medicine, Pregnancy, lcsh:QH301-705.5, Spectroscopy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Chemistry, General Medicine, respiratory system, 3. Good health, Computer Science Applications, Cell biology, Trophoblasts, ARNT, Protein Transport, medicine.anatomical_structure, ontogeny, 030220 oncology & carcinogenesis, CYP1B1, Female, Cell fractionation, Chorionic Villi, Protein Binding, Aryl hydrocarbon receptor nuclear translocator, placenta, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, Placenta, medicine, Animals, Humans, Physical and Theoretical Chemistry, Molecular Biology, Transcription factor, Activator (genetics), Organic Chemistry, AhR, Trophoblast, Aryl hydrocarbon receptor, trophoblast, benzo-a-pyrene, Oxidative Stress, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Gene Expression Regulation, Receptors, Aryl Hydrocarbon, 13. Climate action, biology.protein, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biomarkers
Abstract: International audience; The human placenta is an organ between the blood of the mother and the fetus, which is essential for fetal development. It also plays a role as a selective barrier against environmental pollutants that may bypass epithelial barriers and reach the placenta, with implications for the outcome of pregnancy. The aryl hydrocarbon receptor (AhR) is one of the most important environmental-sensor transcription factors and mediates the metabolism of a wide variety of xenobiotics. Nevertheless, the identification of dietary and endogenous ligands of AhR suggest that it may also fulfil physiological functions with which pollutants may interfere. Placental AhR expression and activity is largely unknown. We established the cartography of AhR expression at transcript and protein levels, its cellular distribution, and its transcriptional activity toward the expression of its main target genes. We studied the profile of AhR expression and activity during different pregnancy periods, during trophoblasts differentiation in vitro, and in a trophoblast cell line. Using diverse methods, such as cell fractionation and immunofluorescence microscopy, we found a constitutive nuclear localization of AhR in every placental model, in the absence of any voluntarily-added exogenous activator. Our data suggest an intrinsic activation of AhR due to the presence of endogenous placental ligands.
Published: 2018

26. An attempt to characterize the human Chorionic Gonadotropin protein by reversed phase liquid chromatography coupled with high-resolution mass spectrometry at the intact level

Author: Nathalie Delaunay, Jean Guibourdenche, Davy Guillarme, Julien Camperi, Audrey Combès, Thierry Fournier, Valérie Pichon, Laboratoires Sciences Analytiques, Bioanalytiques et Miniaturisation, ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Cochin [AP-HP], University of Geneva [Switzerland], Sorbonne Université (SU), Laboratoire Sciences Analytiques, Bioanalytiques, et Miniaturisation (LSABM), Chimie-Biologie-Innovation (UMR 8231) (CBI), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Hôpital Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Gene isoform, endocrine system, Glycosylation, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Liquid chromatography, Pharmaceutical Science, Chorionic Gonadotropin, 01 natural sciences, Data treatment, QTOF high-resolution mass spectrometry, Analytical Chemistry, law.invention, Human chorionic gonadotropin, 03 medical and health sciences, chemistry.chemical_compound, Polysaccharides, Pregnancy, Tandem Mass Spectrometry, law, Drug Discovery, Humans, Protein Isoforms, Spectroscopy, reproductive and urinary physiology, Chromatography, Reverse-Phase, ddc:615, Chromatography, Molecular mass, urogenital system, 010401 analytical chemistry, Intact protein, Reversed-phase chromatography, Repeatability, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 0104 chemical sciences, 030104 developmental biology, chemistry, Human Chorionic Gonadotropin, human Chorionic Gonadotropin, Recombinant DNA, Female, hormones, hormone substitutes, and hormone antagonists
Abstract: International audience; For the first time, the human Chorionic Gonadotropin (hCG) hormone at the intact level was characterized by reversed phase liquid chromatography (RPLC) coupled with high resolution mass spectrometry (HRMS). This heterodimeric protein is specific to human pregnancy, consists in an α and a β subunit, so-called hCGα and hCGβ, respectively, and has 8 glycosylation sites leading to a high number of isoforms. First, the LC method was optimized to separate the largest number of isoforms and also to facilitate the MS ionization process and data treatment. The initial mobile phase composition, slope of the gradient, and column temperature were appropriately selected to maximize the number of separated isoforms. Moreover, the MS detection parameters were adjusted to i) promote the efficient transfer of the heaviest ions, ii) avoid or limit the fragmentation of the ions and iii) improve the sensitivity. The repeatability of the final method in terms of retention times and peak areas was assessed. The method was next used to characterize two hCG-based drugs: Ovitrelle® (a recombinant hCG, r-hCG) and Pregnyl® (hCG isolated from urine of pregnant women, u-hCG). After the deconvolution step, the analytical method did not allow to observe the isoforms of the hCGβ. This may be due to its dramatic higher heterogeneity induced by its 6 glycosylation sites and a lack of ionization in the MS source. Nevertheless, the results revealed the presence of more than 30 hCGα isoforms, which differ by their number and their nature in the two drugs. Then, the molecular weights of the N-glycans already described in the literature for hCG were compiled in a database to identify the hCGα glycoforms by mass matching. This strategy was successfully applied for the identification of five glycoforms for both r-hCG and u-hCG. This work demonstrates for the first time the potential of RPLC-HRMS for the identification of the intact hCGα glycoforms.
Published: 2018

27. Prenatal therapy with pyrimethamine + sulfadiazine vs spiramycin to reduce placental transmission of toxoplasmosis: a multicenter, randomized trial

Author: Laurent Mandelbrot, François Kieffer, Rémi Sitta, Hélène Laurichesse-Delmas, Norbert Winer, Louis Mesnard, Alain Berrebi, Gwenaëlle Le Bouar, Jean-Paul Bory, Anne-Gaëlle Cordier, Yves Ville, Franck Perrotin, Jean-Marie Jouannic, Florence Biquard, Claude d’Ercole, Véronique Houfflin-Debarge, Isabelle Villena, Rodolphe Thiébaut, Denis Pons, C. Nourrisson, Rose-Anne Lavergne, Judith Fillaux, Corinne Assouline, Florence Robert-Gangneux, Coralie L’Ollivier, Florence Bretelle, Béatrice Guidicelli, Patricia Garcia, Anne-Gaelle Cordier, Alexandra Benachi, Christelle Vauloup-Fellous, Emmanuelle Letamendia, Marie-Elisabeth Bougnoux, Nathalie Van Langendonck, Jérôme Potin, Pierre Marty, Christelle Pomarès, Cynthia Trastour, Anne Sophie Deleplancque, Jean-Marc Costa, Marie-Thérèse Chève, Jean-Yves Col, Bernard Cimon, Y. Sterkers, Laurence Lachaud, Gilles Burlet, Martine Maréchaud, Estelle Perraud, Anne-Gaelle Grébille, Morgane Valentin, Sandrine Houzé, Sophie Omnès, Yvon Chitrit, Christine Boissinot, Hélène Yéra, Olivia Anselem, Vassilis Tsatsaris, Marie-Victoire Sénat, Florent Fuchs, Adela Angoulvant, Charles Muszynski, Anne Totet, Catherine Noël, Laurent Bidat, Tiphaine Barjat, Pierre Flori, Hervé Pelloux, Marie-Pierre Brenier-Pinchart, Catherine Thong-Vanh, Corinne Floch, Lionel Carbillon, Eric Lachassine, Aude Ricbourg, Luc Paris, Marc Dommergues, Thierry Rousseau, Frederic Dalle, Marie Laure Dardé, Véronique Aubard, Camille Olivier, Eric Verspyk, Loic Favennec, Service de gynécologie obstétrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Nord Val de Seine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Puériculture et de Périnatalogie, Santé publique et épidémiologie des déterminants professionnels et sociaux de la santé, Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gynécologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Gynécologie‑Obstétrique, Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Universitaire de Reims (CHU Reims), CHRU Tours, Hôpital Bretonneau, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gynécologie-Obstétrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Service de gynécologie-obstétrique, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Université de Bordeaux (UB), Centre de recherche sur la Paléobiodiversité et les Paléoenvironnements (CR2P), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance Publique - Hôpitaux de Marseille (APHM), Gynépole, Aix Marseille Université (AMU)- Hôpital Nord [CHU - APHM], Service de gynécologie-obstétrique, médecine de la reproduction [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Division of Pediatrics and Neonatal Critical Care, FAME Department, South Paris, University Hospitals, 'A.Beclere' Medical Center-APHP, Service de Parasitologie-Mycologie-Médecine Tropicale, CHRU Bretonneau, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Anofel Cryptosporidium National Network, Institut de signalisation, biologie du développement et cancer (ISBDC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Laboratoire de Biologie Moléculaire, Hôpital américain, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Biologie, Génétique et Pathologie des Pathogènes Eucaryotes (MIVEGEC-BioGEPPE), Pathogènes, Environnement, Santé Humaine (EPATH), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), laboratoire parasitologie, CHU Bichat Paris, Ministère de la santé, Hôpital Louis Mourier - AP-HP [Colombes], Service de parasitologie-mycologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service de Gynécologie et Obstétrique [Cochin], Hôpital Cochin [AP-HP], Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gynécologie-Obstétrique [Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de gynécologie-obstétrique et médecine de la reproduction, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Biomécanique et Bioingénierie (BMBI), Université de Technologie de Compiègne (UTC)-Centre National de la Recherche Scientifique (CNRS), Departments of Medical Parasitology and Mycology, Centre Hospitalier René Dubos [Pontoise], Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet [Saint-Étienne] (UJM), Laboratoire de parasitologie-mycologie, CHU Grenoble, Epigenetique, Pathologie et Developpement (UMR_S_741), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de gynécologie-obstétrique [Hôpital Jean Verdier], Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Service de Gynécologie-Obstétrique, Maternité, Chirurgie Gynécologique [CHU Pitié-Salpêtrière], Centre Max Weber (CMW), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Interactions Muqueuses Agents Transmissibles (LIMA), Université de Bourgogne (UB), Service de Gynécologie-Obstétrique [CHU Limoges], CHU Limoges, CHU Tenon [AP-HP], Appareil Digestif Environnement Nutrition (ADEN ), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], CHU Clermont-Ferrand, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional d'Orléans (CHRO), AP-HP - Hôpital Antoine Béclère [Clamart], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), PRES Université Nantes Angers Le Mans (UNAM), CHU Lille, Université de Reims Champagne-Ardenne (URCA), Hôpital Maison Blanche, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Hôpital Paule de Viguier, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Reims Champagne-Ardenne (URCA), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Université Nice Sophia Antipolis (... - 2019) (UNS), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13), Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Gynécologie [CHU Toulouse], Pôle Femme-Mère-Couple [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie et Mycologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Jean Monnet - Saint-Étienne (UJM), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hopital Louis Mourier - AP-HP [Colombes]-Hôpitaux Universitaires Paris Nord Val de Seine, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle de Gynécologie-Obstétrique et Reproduction Humaine, CHU Clermont-Ferrand-Université de Clermont-Ferrand, Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre de recherche Médecine, Science, Santé et Société (CERMES), Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Gynécologie et Obstétrique [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Sud, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Antoine Béclère, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Groupe d'Etude des Interactions Hôte-Parasite (GEIHP), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Hopital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Université Paris 13 (UP13)-Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de Gynécologie et Obstétrique [Groupe Hospitalier Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP], and CHU Tenon [APHP]
Subjects: 0301 basic medicine, Adult, medicine.medical_specialty, 030106 microbiology, Antiprotozoal Agents, Sulfadiazine, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Toxoplasmosis, Congenital, law.invention, 03 medical and health sciences, Folinic acid, pyrimethamine-sulfadiazine, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Humans, 030212 general & internal medicine, Seroconversion, Pregnancy Complications, Infectious, ComputingMilieux_MISCELLANEOUS, spiramycin, prenatal diagnosis, tolerance, business.industry, Spiramycin, Obstetrics and Gynecology, Prenatal Care, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Toxoplasmosis, Infectious Disease Transmission, Vertical, 3. Good health, SISTM, Pyrimethamine, Treatment Outcome, Chemoprophylaxis, Drug Therapy, Combination, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, pregnancy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug, toxoplasmosis
Abstract: International audience; Background - The efficacy of prophylaxis to prevent prenatal toxoplasmosis transmission is controversial, without any previous randomized clinical trial. In France, spiramycin is usually prescribed for maternal seroconversions. A more potent pyrimethamine + sulfadiazine regimen is used to treat congenital toxoplasmosis and is offered in some countries as prophylaxis. Objective - We sought to compare the efficacy and tolerance of pyrimethamine + sulfadiazine vs spiramycin to reduce placental transmission. Study design - This was a randomized, open-label trial in 36 French centers, comparing pyrimethamine (50 mg qd) + sulfadiazine (1 g tid) with folinic acid vs spiramycin (1 g tid) following toxoplasmosis seroconversion. Results - In all, 143 women were randomized from November 2010 through January 2014. An amniocentesis was later performed in 131 cases, with a positive Toxoplasma gondii polymerase chain reaction in 7/67 (10.4%) in the pyrimethamine + sulfadiazine group vs 13/64 (20.3%) in the spiramycin group. Cerebral ultrasound anomalies appeared in 0/73 fetuses in the pyrimethamine + sulfadiazine group, vs 6/70 in the spiramycin group (P = .01). Two of these pregnancies were terminated. Transmission rates, excluding 18 children with undefined status, were 12/65 in the pyrimethamine + sulfadiazine group (18.5%), vs 18/60 in the spiramycin group (30%, P = .147), equivalent to an odds ratio of 0.53 (95% confidence interval, 0.23-1.22) and which after adjustment tended to be stronger (P = .03 for interaction) when treatment started within 3 weeks of seroconversion (95% confidence interval, 0.00-1.63). Two women had severe rashes, both with pyrimethamine + sulfadiazine. Conclusion - There was a trend toward lower transmission with pyrimethamine + sulfadiazine, but it did not reach statistical significance, possibly for lack of statistical power because enrollment was discontinued. There were also no fetal cerebral toxoplasmosis lesions in the pyrimethamine + sulfadiazine group. These promising results encourage further research on chemoprophylaxis to prevent congenital toxoplasmosis.
Published: 2018

28. Local outbreak of Clostridioides difficile PCR-Ribotype 018 investigated by multi locus variable number tandem repeat analysis, whole genome multi locus sequence typing and core genome single nucleotide polymorphism typing

Author: Rabab Syed Zaidi, Thierry Lavigne, Béatrice Turcan, Cécile Gateau, Stéphanie Deboscker, Jeanne Couturier, Joris Muller, Céline Ménard, Anlyata Youssouf, Thomas Vogel, Frédéric Barbut, Elise Schmitt, Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Strasbourg, and CCSD, Accord Elsevier
Subjects: DNA, Bacterial, [SDV]Life Sciences [q-bio], PCR-Ribotyping, Bacterial Toxins, Single-nucleotide polymorphism, Locus (genetics), Microbial Sensitivity Tests, Minisatellite Repeats, Biology, Multiple Loci VNTR Analysis, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Ribotyping, Microbiology, Genome, Disease Outbreaks, 03 medical and health sciences, Tandem repeat, Humans, cgSNP, Typing, Phylogeny, 030304 developmental biology, Genetics, 0303 health sciences, Clostridioides difficile, 030306 microbiology, MLVA, Outbreak, Genomics, wgMLST, Anti-Bacterial Agents, 3. Good health, [SDV] Life Sciences [q-bio], Variable number tandem repeat, Infectious Diseases, Clostridium Infections, C. difficile, Genome, Bacterial, Multilocus Sequence Typing
Abstract: International audience; The prevalence of Clostridioides difficile PCR-ribotype (RT) 018 is low in Europe but variations are observed across countries. We report here the first RT 018-related outbreak in France that took place in 4 geriatric units (GU) in Strasbourg, France. From January to December 2017, 38 patients were diagnosed with C. difficile infection (CDI). Strains were first characterized by PCR ribotyping: 19 out of 38 (50%) strains belonged to RT 018. These strains as well as 12 RT 018 isolated in other French healthcare facilities and 2 strains of RT 018 isolated in the GU in 2015 were characterized by multi locus variable-number tandem repeat (VNTR) analysis (MLVA), whole genome multi locus sequence typing (wgMLST) and core genome single nucleotide polymorphism typing (cgSNP). The MLVA indicated that 15 out of 19 epidemic strains of RT 018 were included in 2 Clonal Complexes (CC). Four RT 018 strains from the outbreak did not belong to the CC. The wgMLST and cgSNP typing analysis revealed a single CC that included 19 strains from the geriatric unit (17 from GU in 2017 and 2 from GU in 2015) and 4 strains (33%) from other healthcare facilities (HCF). Our results suggest that a specific RT 018 clone has spread in the geriatric unit and has evolved slowly over time. MLVA, wgMLST and cgSNP typing results provided fairly consistent information but wgMLST and cgSNP typing better separated epidemic strains from non-epidemic strains. Compared to wgMLST, the cgSNP typing did not provide additional information.
Published: 2019

29. Liposomes as Gene Delivery Vectors for Human Placental Cells

Author: Lucie Valero, Jeanne Leblond, Thierry Fournier, Caroline Roques, Danielle Campiol Arruda, Virginie Escriou, Karine Andrieux, Nathalie Mignet, Audrey Chissey, Khair Alhareth, Warren Viricel, Jenifer Espinoza Romero, Hélène Dhotel, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Faculty of Pharmacy [Montréal, QC, Canada], Université de Montréal (UdeM), Physiopathologie et pharmacotoxicologie placentaire humaine : Microbiote pré & post natal (3PHM - UMR-S 1139), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Service de Chimie Moléculaire (SCM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mignet, Nathalie, Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), CAMPIOL ARRUDA, DANIELLE, Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Faculty of Pharmacy, University of Montreal
Subjects: liposomes, Small interfering RNA, placenta, Genetic enhancement, media_common.quotation_subject, Genetic Vectors, Pharmaceutical Science, 02 engineering and technology, Gene delivery, primary trophoblast cells, Analytical Chemistry, lcsh:QD241-441, 03 medical and health sciences, 0302 clinical medicine, lcsh:Organic chemistry, Pregnancy, Placenta, Drug Discovery, medicine, Humans, RNA, Small Interfering, Physical and Theoretical Chemistry, Internalization, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, media_common, Liposome, 030219 obstetrics & reproductive medicine, Chemistry, Communication, Organic Chemistry, Gene Transfer Techniques, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 021001 nanoscience & nanotechnology, Molecular biology, Trophoblasts, 3. Good health, Pregnancy Complications, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Nanomedicine, medicine.anatomical_structure, Chemistry (miscellaneous), Lipofectamine, siRNA, Nucleic acid, Molecular Medicine, Female, 0210 nano-technology
Abstract: Nanomedicine as a therapeutic approach for pregnancy-related diseases could offer improved treatments for the mother while avoiding side effects for the fetus. In this study, we evaluated the potential of liposomes as carriers for small interfering RNAs to placental cells. Three neutral formulations carrying rhodamine-labelled siRNAs were evaluated on an in vitro model, i.e., human primary villous cytotrophoblasts. siRNA internalization rate from lipoplexes were compared to the one in the presence of the lipofectamine reagent and assessed by confocal microscopy. Results showed cellular internalization of nucleic acid with all three formulations, based on two cationic lipids, either DMAPAP or CSL-3. Moreover, incubation with DMAPAP+AA provided a rate of labelled cells as high as with lipofectamine (53 ± 15% and 44 ± 12%, respectively) while being more biocompatible. The proportion of cells which internalized siRNA were similar when using DMAPAP/DDSTU (16 ± 5%) and CSL-3 (22 ± 5%). This work highlights that liposomes could be a promising approach for gene therapy dedicated to pregnant patients.
Published: 2018

30. Intrauterine fetal deaths related to antiphospholipid syndrome: a descriptive study of 65 women

Author: Belhocine, Mériem, Coutte, Laetitia, Martin Silva, Nicolas, Morel, Nathalie, Guettrot-Imbert, Gaëlle, Paule, Romain, Le Jeunne, Claire, Fredi, Micaela, Dreyfus, Michel, Piette, Jean-Charles, Souchaud-Debouverie, Odile, Deneux-Tharaux, Catherine, Tsatsaris, Vassilis, Pannier, Emmanuelle, Le Guern, Veronique, Costedoat-Chalumeau, Nathalie, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Cochin [AP-HP], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Gynécologie-Obstétrique et Médecine de la Reproduction [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gynécologie et Obstétrique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, lcsh:Diseases of the musculoskeletal system, [SDV]Life Sciences [q-bio], Lupus, Thrombosis, Preeclampsia, HELLP, Pregnancy Complications, Pregnancy, Antiphospholipid syndrome, Antibodies, Antiphospholipid, Humans, Intrauterine fetal death, Female, France, lcsh:RC925-935, Fetal Death, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article, Follow-Up Studies, Retrospective Studies
Abstract: International audience; ObjectiveAlthough one of the three obstetric manifestations of antiphospholipid syndrome (APS) is intrauterine fetal death (IUFD), little is known about it in this context. We report the first large series of patients with APS and IUFD.MethodsWe retrospectively analyzed the history and clinical data of women at four French hospitals. All had (1) APS diagnosis (Sydney criteria) and (2) IUFD at or after 10 weeks of gestation (weeks) between 2000 and 2016.ResultsThe study included 65 women. Their median age at the index IUFD was 29 years (IQR 26–33); 38 (58%) were primigravidas. The index IUFD was the first APS clinical manifestation in 48 women (74%). Overall, 35% had a triple-positive antibody profile.IUFD occurred at a median gestational age of 24 weeks (IQR 18–27) and was associated with maternal obstetric complications in 16 women (25%), namely, preeclampsia (n = 12), hemolysis, elevated liver enzymes, and low platelet syndrome (HELLP) (n = 6), and/or placental abruption (n = 5). Half of the 50 women with available data had a small-for-gestational-age fetus.Overall, including during the follow-up period of 4 years (IQR 2–9), 28 women (43%) had at least one thrombosis, and 29% were diagnosed with systemic lupus erythematosus (SLE). Ultimately, 54 women (83%) had at least one live birth. Only one woman had three consecutive early miscarriages.ConclusionIUFD was most often the inaugural sign of APS. Of the APS classification criteria, IUFD, preeclampsia, and thromboses were common in this cohort, while the “3 consecutive early miscarriages” criterion was met only once. With treatment, most of the women successfully had at least one live birth.
Published: 2018

31. New Transcriptional Reporters to Quantify and Monitor PPARγ Activity

Author: Thierry Fournier, Séverine A. Degrelle, Hussein Shoaito, Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), PremUp Foundation, Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by ANSES (PhthalatPreG project)., DEGRELLE, Séverine, and Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Reporter gene, Cell type, Article Subject, SUPERFAMILY, Lipid metabolism, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell biology, 03 medical and health sciences, 030104 developmental biology, Nuclear receptor, lcsh:Biology (General), Adipogenesis, Drug Discovery, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Pharmacology (medical), lipids (amino acids, peptides, and proteins), lcsh:QH301-705.5, Research Article
Abstract: The peroxisome-proliferator-activated-receptor-γ (PPARγ) is a member of the nuclear receptor superfamily that plays a critical role in diverse biological processes, including adipogenesis, lipid metabolism, and placental development. To study the activity of PPARγ, we constructed two new reporter genes: a fluorescent GFP-tagged histone-2B (PPRE-H2B-eGFP) and a secreted nanoluciferase (PPRE-pNL1.3[secNluc]). This study demonstrates their usage to monitor PPARγ activity in different cell types and screen for PPARγ’s potential ligands.
Published: 2017

32. The Accuracy of Large Loop Excision of the Transformation Zone Specimen Dimensions in Determining Volume

Author: Carcopino, Xavier, Mancini, Julien, Prendiville, Walter, Gondry, Jean, Chevreau, Julien, Lamblin, Gery, Atallah, Anthony, Lavoué, Vincent, Caradec, Claire, Baldauf, Jean-Jacques, Bryand, Angélique, Henno, Sébastien, Agostini, Aubert, Douvier, Serge, Jarniat, Adelaïde, Riethmuller, Didier, Mendel, Anne, Brun, Jean-Luc, Rakotomahenina, Hajanarina, Preaubert, Lise, Hôpital Nord [CHU - APHM], Service d'Obstétrique-Gynécologie [Marseille], Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille- Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre international de Recherche sur le Cancer (CIRC), Membranes et cibles thérapeutiques (MCT), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées (IRBA), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Service de gynécologie–obstétrique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Département de Gynécologie-Obstétrique [CHU Strasbourg], Assistance Publique - Hôpitaux de Marseille (APHM), Service de Gynécologie Obstétrique, Médecine Foetale et Stérilité Conjugale - Chirurgie Gynécologie et Oncologique [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Gynécologie Obstétrique [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Bordeaux [Bordeaux], Dupuis, Christine, Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Département Gynécologie et oncologie [CHU Dijon], Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées (IRBA)-Aix Marseille Université (AMU), Service de Gynécologie et Obstétrique [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Unité de soins obstétricaux [CHRU Besançon] (Pôle Mère-Femme), and Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: International audience; Objective: The aim of the study was to determine which mathematical formula of specimen dimensions is the most accurate method of determining volume of the excised specimen at loop excision of the transformation zone.Materials and methods: A multicenter prospective observational study was conducted. A total of 258 patients who had a loop excision of the transformation zone performed as treatment of cervical intraepithelial neoplasia 2-3 were included. The dimensions and the volume of the specimen were measured at the time of the procedure, before formaldehyde fixation. The volume was measured by immersing the specimen in a graduated cylinder using Archimedes fluid displacement technique. The measured volume was compared with the calculated volume using different volume formulas, that is, a cone, a cylinder, a parallelepiped, and a hemiellipsoid. The main outcome measure was the relationship between calculated volume (using the dimensions of thickness, length, and circumference) and the measured volume of the specimen.Results: The mean (SD) thickness, length, and circumference of specimens were 8.8 mm (3.8), 12.7 mm (5.9), and 45.7 mm (16.8), respectively. The mean (SD) measured volume was 2.53 (1.49) mL. Using the formula for the volume of a cone, a cylinder, a parallelepiped and a hemiellipsoid, estimated volumes were 1.03 mL (1.22), 3.10 mL (3.65), 6.20 mL (7.31), and 2.07 mL (2.44), respectively. The highest intraclass correlation coefficient between measured and calculated volume was observed when using the formula for the volume of a hemiellipsoid specimen (0.47, 95% CI = 0.36-0.56).Conclusions: The hemiellipsoid formula is the most accurate determinant of the excised volume. Other formulas do not allow for an accurate estimation of the excised volume.
Published: 2017

33. The use of electroporation in developmental biology

Author: Séverine A. Degrelle, Aitana Perea-Gomez, Elsa Mazari, Diana Suárez-Boomgaard, Charlie Gosse, Isabelle Hue, Isabelle Migeotte, Xuan Zhao, Laboratoire de Photonique et de Nanostructures, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université libre de Bruxelles (ULB), Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Université Paris-Saclay, Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), Université Paris Descartes - Paris 5 (UPD5), Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), U 1091, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nice Sophia-Antipolis (UNSA), University of Tokyo, 'ElectroMice' (CNRS PI: Physique Chimie Biologie 2008), 'Electro- TagMam' (Cnano IdF 2011), ' ElectroDev ' (PHC Tournesol 2014), 'RhoGTPases and collective migration' (FNRS MIS 2013), Université Libre de Bruxelles [Bruxelles] (ULB), Biologie du développement et reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Université de Lille, Sciences Humaines et Sociales, Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire ( IRIBHM ), Université Libre de Bruxelles [Bruxelles] ( ULB ), Biologie du développement et reproduction ( BDR ), Institut National de la Recherche Agronomique ( INRA ) -Ecole Nationale Vétérinaire d'Alfort-Centre National de la Recherche Scientifique ( CNRS ), Physiopathologie et Pharmacotoxicologie Placentaire Humaine, UMR-S1139, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Sorbonne Paris Cité ( USPC ), Université Paris Descartes - Paris 5 ( UPD5 ), UMR 7277, Centre National de la Recherche Scientifique ( CNRS ), Institut de Biologie Valrose ( IBV ), and Université de Nice - Sophia Antipolis ( UNSA )
Subjects: 0301 basic medicine, 0303 health sciences, genetic engineering, électroporation, Electroporation, organogenesis, 030302 biochemistry & molecular biology, embryogénèse, Biology, Cell biology, numerical simulations, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, embryogenesis, organogénèse, [ SDV.BDD ] Life Sciences [q-bio]/Development Biology, Developmental biology, [SDV.BDD]Life Sciences [q-bio]/Development Biology, 030217 neurology & neurosurgery, microfabrication, cell labeling, 030304 developmental biology
Abstract: Chapter 139-1; During the formation of a complex organism, cells divide, die, migrate, and differentiate. Biologists have established tools to observe those phenomena but also to change their course, which subsequently enables to infer causal relationships between various events occurring in different cell groups. More precisely, present approaches mostly rely on modifications of gene expression. For instance, cells are labeled with fluorescent proteins and tracked within the embryo, molecular signals are switched on and off to perturb regulatory pathways. Importantly, in all those experiments, the exogenous genetic material must be delivered at the right place and with the appropriate timing: requirements that can both be fulfilled by electroporation. After 15 years of constant refinement, this technique has now superseded methods like viral infection, microinjection, and lipofection. Applications encompass a large number of model organisms, targeted anatomical structures, and molecular biology techniques.
Published: 2017

34. The early pregnancy placenta foreshadows dna methylation alterations of solid tumors

Author: David Klatzmann, Djamel Nehar-Belaid, Dominique Bellet, Thierry Fournier, Virginie Dangles-Marie, Martin J. Aryee, Akpeli V. Nordor, Sophie Richon, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux (Inserm U745), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biothérapies [CHU Pitié-Salpétrière], Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Département de Recherche Translationnelle, Institut Curie [Paris], Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Massachusetts General Hospital [Boston], Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], KLATZMANN, DAVID, CHU Pitié-Salpêtrière [AP-HP], Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux ( Inserm U745 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Laboratoire de génétique moléculaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), INSTITUT CURIE, La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus ( UMR_S 767 ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)
Subjects: 0301 basic medicine, Cancer Research, medicine.disease_cause, Epigenesis, Genetic, Pregnancy, ComputingMilieux_MISCELLANEOUS, Epigenomics, DNA methylation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, CANCER, 3. Good health, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Pregnancy Trimester, Second, embryonic structures, Chorionic villi, GROWTH, Female, Research Paper, GENES, placenta, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, TROPHOBLAST, [SDV.CAN] Life Sciences [q-bio]/Cancer, INFLAMMATION, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Placenta, medicine, Humans, Neoplastic transformation, 5-METHYLCYTOSINE, Epigenetics, REGULATORY T-CELLS, Molecular Biology, PURIFICATION, epigenetics, Carcinoma, Placentation, Pregnancy Trimester, First, 030104 developmental biology, Immunology, epigenomics, Cancer research, HYPOMETHYLATED BLOCKS, IMPLANTATION, Carcinogenesis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, hypomethylation
Abstract: International audience; The placenta relies on phenotypes that are characteristic of cancer to successfully implant the embryo in the uterus during early pregnancy. Notably, it has to invade its host tissues, promote angiogenesis—while surviving hypoxia—, and escape the immune system. Similarities in DNA methylation patterns between the placenta and cancers suggest that common epigenetic mechanisms may be involved in regulating these behaviors. We show here that megabase-scale patterns of hypomethylation distinguish first from third trimester chorionic villi in the placenta, and that these patterns mirror those that distinguish many tumors from corresponding normal tissues. We confirmed these findings in villous cytotrophoblasts isolated from the placenta and identified a time window at the end of the first trimester, when these cells come into contact with maternal blood, as the likely time period for the methylome alterations. Furthermore, the large genomic regions affected by these patterns of hypomethylation encompass genes involved in pathways related to epithelial-mesenchymal transition, immune response, and inflammation. Analyses of expression profiles corresponding to genes in these hypomethylated regions in colon adenocarcinoma tumors point to networks of differentially expressed genes previously implicated in carcinogenesis and placentogenesis, where nuclear factor kappa B is a key hub. Taken together, our results suggest the existence of epigenetic switches involving large-scale changes of methylation in the placenta during pregnancy and in tumors during neoplastic transformation. The characterization of such epigenetic switches might lead to the identification of biomarkers and drug targets in oncology as well as in obstetrics and gynecology.
Published: 2017

35. Gestational age-related patterns of AMOT methylation are revealed in preterm infant endothelial progenitors

Author: Florent Dumont, Farid Boubred, Thierry Fournier, G. Vinci, Christophe Buffat, Françoise Dignat-George, Stéphanie Simoncini, Isabelle Ligi, Daniel Vaiman, Bernard Le Bonniec, Umberto Simeoni, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Caen Normandie - UFR Santé (UNICAEN Santé), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Innovations thérapeutiques en hémostase (IThEM - U1140), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), and Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Male, Angiogenesis, Physiology, lcsh:Medicine, Blood Pressure, Cardiovascular Physiology, Biochemistry, Vascular Medicine, Epigenesis, Genetic, 0302 clinical medicine, Medicine and Health Sciences, Medicine, lcsh:Science, Promoter Regions, Genetic, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Endothelial Progenitor Cells, Multidisciplinary, DNA methylation, Microfilament Proteins, Gestational age, Methylation, Fetal Blood, Chromatin, Body Fluids, Nucleic acids, Blood, CpG site, 030220 oncology & carcinogenesis, Cord blood, Infant, Small for Gestational Age, Hypertension, Intercellular Signaling Peptides and Proteins, Female, Epigenetics, Anatomy, DNA modification, Infant, Premature, Chromatin modification, Maternal Age, Research Article, Chromosome biology, Adult, Cell biology, Real-Time Polymerase Chain Reaction, Andrology, 03 medical and health sciences, Vasculogenesis, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], CpG Islands, DNA Methylation, Endothelial Progenitor Cells/metabolism, Fetal Blood/metabolism, Humans, Infant, Premature/growth & development, Infant, Premature/metabolism, Infant, Small for Gestational Age/growth & development, Infant, Small for Gestational Age/metabolism, Intercellular Signaling Peptides and Proteins/genetics, Intercellular Signaling Peptides and Proteins/metabolism, Membrane Proteins/genetics, Membrane Proteins/metabolism, Sequence Analysis, DNA, Genetics, Treatment Guidelines, Health Care Policy, Biology and life sciences, business.industry, lcsh:R, Membrane Proteins, Neonates, DNA, Health Care, 030104 developmental biology, Angiomotins, lcsh:Q, Gene expression, business, Developmental Biology
Abstract: International audience; Objective: Preterm birth is associated with altered angiogenesis and with increased risk of cardiovascular dysfunction and hypertension at adulthood. We previously demonstrated that in preterm newborns circulating cord blood endothelial progenitor cells (ECFC), responsible for angio/vasculogenesis, are reduced in number and display altered angiogenic properties. Altered angiogenic function was associated with a decreased expression of pro-angiogenic genes, among which the AMOT gene which is a strong positive regulator of angiogenesis. Such dysregulation may be related to epigenetic factors. In this study we analyse the methylation profiling of the AMOT gene during development, through a comparative analysis of the cord blood ECFC of preterm newborns and their term counterpart.Methods: We used both cloning-sequencing and pyrosequencing experiments to perform a comparative analysis of the DNA methylation profile of the promoter CpG island of AMOT gene in the cord blood ECFC of 16 preterm newborns (28–35 weeks gestational age-GA) and 15 term newborns (>37 weeks GA).Results: Twenty nine clones (obtained from 2 term newborns) and forty clones (obtained from 3 preterm newborns) were sequenced. The AMOT gene methylation rate was significantly higher in preterm compared to term newborns (4.5% versus 2.5% respectively: χ2 = 3.84; P = 1.8 10−02). Bisulfite pyrosequencing identified four CpG dinucleotides with significantly higher methylation levels in preterm newborns. This CpG-targeted methylation significantly decreased with increasing gestational age.Conclusions: These findings highlight importance of pro-angiogenic AMOT gene methylation in ECFC, suggesting that epigenetic mechanisms may control the regulation of angiogenesis during development. Therefore they pave the way to specific short term and long term complications of preterm birth by altered angiogenesis.
Published: 2017

36. Dynamic Pattern of HOXB9 Protein Localization during Oocyte Maturation and Early Embryonic Development in Mammals

Author: Caroline Sauvegarde, René Rezsohazy, Delphine Paul, Isabelle Donnay, Laure Bridoux, Alice Jouneau, Isabelle Hue, Séverine A. Degrelle, Biologie Moléculaire et Cellulaire Animale [Louvain-la-Neuve, Belgium] (BMCA), Université Catholique de Louvain = Catholic University of Louvain (UCL)-Institut des Sciences de la Vie [Louvain-la-Neuve, Belgium], CHU Pontchaillou [Rennes], Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by a FRFC grant from Fonds National de la Recherche Scientifique (Belgium – Grant number : 2.4566.07), Action de Recherche Concertée from the Communauté française (Belgium), STSM grant from COST Action FA0702 (Gemini)., Université Catholique de Louvain (UCL)-Institut des Sciences de la Vie [Louvain-la-Neuve, Belgium], Institut National de la Recherche Agronomique (INRA)-Institut National Agronomique Paris-Grignon (INA P-G), UMR INRA-ENVA 1198 (BDR), École nationale vétérinaire d'Alfort (ENVA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), UCL - SST/ISV - Institut des sciences de la vie, École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and DEGRELLE, Séverine
Subjects: 0301 basic medicine, Embryology, Zygote, lcsh:Medicine, Fluorescent Antibody Technique, Gene Expression, maturation ovocytaire, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Gene Knockout Techniques, Mice, Oogenesis, 0302 clinical medicine, Animal Cells, Inner cell mass, hoxb9, bovine embryo, endoderm, lcsh:Science, Staining, Mammals, 030219 obstetrics & reproductive medicine, Multidisciplinary, Biologie du développement, Cell Staining, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, mammifère, Embryo, Immunohistochemistry, Development Biology, Protein Transport, medicine.anatomical_structure, OVA, embryonic structures, Cellular Types, Endoderm, Research Article, production d'embryon, Embryonic Development, Biology, Research and Analysis Methods, 03 medical and health sciences, Fetus, medicine, Animals, Humans, Cell Lineage, Blastocyst, Immunohistochemistry Techniques, Cytoplasmic Staining, Homeodomain Proteins, lcsh:R, Embryos, Gastrulation, Embryogenesis, Biology and Life Sciences, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, Oocyte, Molecular biology, Nuclear Staining, Histochemistry and Cytochemistry Techniques, Germ Cells, 030104 developmental biology, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Specimen Preparation and Treatment, développement embryonnaire, Epiblast, embryon, Oocytes, Immunologic Techniques, lcsh:Q, Blastocysts, Cattle, Developmental Biology
Abstract: International audience; BACKGROUND:We previously showed that the homeodomain transcription factor HOXB9 is expressed in mammalian oocytes and early embryos. However, a systematic and exhaustive study of the localization of the HOXB9 protein, and HOX proteins in general, during mammalian early embryonic development has so far never been performed.RESULTS:The distribution of HOXB9 proteins in oocytes and the early embryo was characterized by immunofluorescence from the immature oocyte stage to the peri-gastrulation period in both the mouse and the bovine. HOXB9 was detected at all studied stages with a dynamic expression pattern. Its distribution was well conserved between the two species until the blastocyst stage and was mainly nuclear. From that stage on, trophoblastic cells always showed a strong nuclear staining, while the inner cell mass and the derived cell lines showed important dynamic variations both in staining intensity and in intra-cellular localization. Indeed, HOXB9 appeared to be progressively downregulated in epiblast cells and only reappeared after gastrulation had well progressed. The protein was also detected in the primitive endoderm and its derivatives with a distinctive presence in apical vacuoles of mouse visceral endoderm cells.CONCLUSIONS:Together, these results could suggest the existence of unsuspected functions for HOXB9 during early embryonic development in mammals.
Published: 2016

37. Fluid Shear Stress Promotes Placental Growth Factor Upregulation in Human Syncytiotrophoblast Through the cAMP-PKA Signaling Pathway

Author: Thierry Fournier, Audrey Chissey, Anthony Atallah, Jean Guibourdenche, Sarah Vieillefosse, Vassilis Tsatsaris, Bassam Haddad, Guillaume Pidoux, Edouard Lecarpentier, Abdul I. Barakat, Danièle Evain-Brion, Marylise Hebert-Schuster, Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Pidoux, Guillaume
Subjects: 0301 basic medicine, Placental growth factor, placental growth factor, [SDV]Life Sciences [q-bio], Placenta, Syncytiotrophoblasts, cell extracts, 7. Clean energy, 0302 clinical medicine, Pregnancy, Cyclic AMP Response Element-Binding Protein, Cells, Cultured, 030219 obstetrics & reproductive medicine, phosphorylation, Immunohistochemistry, Cell biology, Trophoblasts, Up-Regulation, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Female, Intracellular, Signal Transduction, medicine.medical_specialty, Immunoblotting, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, calcium signaling, Real-Time Polymerase Chain Reaction, 03 medical and health sciences, Paracrine signalling, Syncytiotrophoblast, Downregulation and upregulation, Internal medicine, Internal Medicine, medicine, Humans, RNA, Messenger, Protein kinase A, Autocrine signalling, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, Placenta Growth Factor, Analysis of Variance, Membrane Proteins, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, trophoblast, 030104 developmental biology, Endocrinology, Stress, Mechanical
Abstract: The effects of fluid shear stress (FSS) on the human syncytiotrophoblast and its biological functions have never been studied. During pregnancy, the syncytiotrophoblast is the main source of placental growth factor (PlGF), a proangiogenic factor involved in the placental angiogenesis and the vascular adaptation to pregnancy. The role of FSS in regulating PlGF expression in syncytiotrophoblasts is unknown. We investigated the impact of FSS on the production and secretion of the PlGF by the human syncytiotrophoblasts in primary cell culture. Laminar and continuous FSS (1 dyn cm −2 ) was applied to human syncytiotrophoblasts cultured in a parallel-plate flow chambers. Secreted levels of PlGF, sFlt-1 (soluble fms-like tyrosin kinase-1), and prostaglandin E2 were tested by immunologic assay. PlGF levels of mRNA and intracellular protein were examined by RT-PCR and Western blot, respectively. Intracellular cAMP levels were examined by time-resolved fluorescence resonance energy transfer cAMP accumulation assay. Production of cAMP and PlGF secretion was significantly increased in FSS conditions compared with static conditions. Western blot analysis of cell extracts exposed to FSS showed an increased phosphorylation of protein kinase A substrates and cAMP response element-binding protein on serine 133. FSS-induced phosphorylation of cAMP response element-binding protein and upregulation of PlGF were prevented by inhibition of protein kinase A with H89 (3 μmol/L). FSS also triggers intracellular calcium flux, which increases the synthesis and release of prostaglandin E2. The enhanced intracellular cAMP in FSS conditions was blocked by COX1/COX2 (cyclooxygenase) inhibitors, suggesting that the increase in prostaglandin E2 production could activate the cAMP/protein kinase A pathway in an autocrine/paracrine fashion. FSS activates the cAMP/protein kinase A pathway leading to upregulation of PlGF in human syncytiotrophoblast.
Published: 2016

38. Are Host Genetics the Predominant Determinant of Persistent NasalStaphylococcus aureusCarriage in Humans?

Author: Cécile Angebault, François Rousset, Loïc Epelboin, Claire Dupont, Assiya El Miniai, Olivier Clermont, Sophie Jarraud, Alex van Belkum, Brandusa Elena Lixandru Lixandru, Raymond Ruimy, Mélanie Bertine, Gilles Peroz, Mehri Tavakol, Gerard Lina, Magaly Renard, Mathilde Lescat, Félix Djossou, Laurence Armand Lefevre, Régis Marc Bettinger, Antoine Andremont, Michèle Bes, François Vandenesch, Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Service de médecine interne et maladies tropicales, CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, laboratoire de biomécanique et bioinginérie, Laboratoire de mécanique des solides (LMS), École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris-Centre National de la Recherche Scientifique (CNRS), Unité des Maladies Infectieuses et Tropicales (UMIT), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Université de Guyane (UG), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Staphylocoques, Hospices Civils de Lyon (HCL), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathogenie des Staphylocoques, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), R&D Microbiologie, bioMerieux SA, BIOMERIEUX, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Emergence de la résistance bactérienne in vivo (EA3964), Université Paris Diderot - Paris 7 (UPD7), Developmental Biology, Medical Microbiology & Infectious Diseases, École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)
Subjects: Male, Rural Population, [SDV]Life Sciences [q-bio], Prevalence, MESH: Staphylococcus aureus/isolation & purification, medicine.disease_cause, Gene Frequency, Risk Factors, Polymorphism (computer science), Genotype, Immunology and Allergy, Aged, 80 and over, Genetics, 0303 health sciences, education.field_of_study, Epidemiological Factors, Middle Aged, Staphylococcal Infections, Bacterial Typing Techniques, 3. Good health, C-Reactive Protein, Infectious Diseases, Staphylococcus aureus, Carrier State, Female, Nasal Cavity, MESH: Nasal Cavity/microbiology, Adult, Adolescent, Population, Single-nucleotide polymorphism, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Microbiology, Young Adult, 03 medical and health sciences, medicine, Humans, education, Aged, MESH: Staphylococcal Infections/genetics, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Polymorphism, Genetic, 030306 microbiology, Indians, South American, DNA Fingerprinting, MESH: Carrier State/microbiology, Carriage, Interleukin-4, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background. Staphylococcus aureus nasal carriage is influenced by multifactorial interactions which are difficult to study in open populations. Therefore, we concomitantly assessed the epidemiological, microbiological, and human-genetic carriage-related factors in a nearly closed population. Methods. In 2006 and 2008, we collected nasal S. aureus strains, human DNA, and epidemiological data from 154 adult Wayampi Amerindians living in an isolated village in the Amazonian forest. The genetics of the strains (multilocus sequence type, spa type, and toxin-content type), epidemiological risk factors, antibiotic exposure, and allelic polymorphism of human genes putatively involved in carriage of the persistent carriers were compared with those of other volunteers. Results. Overall carriage prevalence was 41.7% in 2006 and 57.8% in 2008, but the overall prevalence of persistent carriage was only 26%. The rare and phylogenetically distant multilocus sequence type ST1223 was present in 18.5% of the carriers in 2006 and 34.8% in 2008. No epidemiological factors or antibiotic exposure were significantly associated with persistent carriage, but single nucleotide polymorphism distribution in C-reactive proteins C2042T and C1184T and interleukin-4 C524T genes was significantly associated (P=.02, by global test). Conclusion. Host genetic factors appeared to be the predominant determinant for S. aureus persistent nasal carriage in humans.
Published: 2010

39. Annexin-A5 promotes membrane resealing in human trophoblasts

Author: Céline Gounou, Danièle Evain-Brion, Anthony Bouter, Laurent Plawinski, Romain Carmeille, Séverine A. Degrelle, Flora Bouvet, Alain Brisson, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), PremUp Foundation, Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), The project was supported by ANR (grant ANR-11-BSV1-0035 to A.R.B.) and by AFM-Téléthon (grant AFM-téléthon17140 to A.B.)., ANR-11-BSV1-0035,PlacentA5,Rôle de l'Annexine-A5 dans la réparation et la régénération du placenta humain(2011), DEGRELLE, Séverine, BLANC - Rôle de l'Annexine-A5 dans la réparation et la régénération du placenta humain - - PlacentA52011 - ANR-11-BSV1-0035 - BLANC - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), and Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Placenta, Syncytiotrophoblasts, Membrane repair, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, Lesion removal, Annexin-A5, Membrane resealing, Cell membrane, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pregnancy, Cell Line, Tumor, medicine, Extracellular, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Humans, Annexin A5, Molecular Biology, reproductive and urinary physiology, 030304 developmental biology, 0303 health sciences, Cell Membrane, Trophoblast, Cell Biology, Phosphatidylserine, Trophoblasts, Cell biology, Membrane, medicine.anatomical_structure, chemistry, Biochemistry, 030220 oncology & carcinogenesis, embryonic structures, Female, Cytotrophoblasts
Abstract: International audience; Annexin-A5 (AnxA5) is the smallest member of the annexins, a group of soluble proteins that bind to membranes containing negatively-charged phospholipids, principally phosphatidylserine, in a Ca 2+-dependent manner. AnxA5 presents unique properties of binding and self-assembling on membrane surfaces, forming highly ordered two-dimensional (2D) arrays. We showed previously that AnxA5 plays a central role in the machinery of cell membrane repair of murine perivascular cells, promoting the resealing of membrane damages via the formation of 2D protein arrays at membrane disrupted sites and preventing the extension of membrane ruptures. As the placenta is one of the richest source of AnxA5 in humans, we investigated whether AnxA5 was involved in membrane repair in this organ. We addressed this question at the level of human trophoblasts, either mononucleated cytotrophoblasts or multinucleated syncytiotrophoblasts, in choriocarcinoma cells and primary trophoblasts. Using established procedure of laser irradiation and fluorescence microscopy, we observed that both human cytotrophoblasts and syncytiotrophoblasts repair efficiently a μm 2-size disruption. Compared to wild-type cells, AnxA5-deficient trophoblasts exhibit severe defect of membrane repair. Through specifically binding to the disrupted site as early as a few seconds after membrane wounding, AnxA5 promotes membrane resealing of injured human trophoblasts. In addition, we observed that a large membrane area containing the disrupted site was released in the extracellular milieu. We propose mechanisms ensuring membrane resealing and subsequent lesion removal in human trophoblasts. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.
Published: 2015

40. Spatiotemporal regulation of cAMP signaling controls the human trophoblast fusion

Author: Pascale Gerbaud, Guillaume Pidoux, Kjetil Taskén, Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oslo (UiO), Oslo University Hospital [Oslo], La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Pharmacie, Université Paris-Sud - Paris 11 (UP11), Signalisation et physiopathologie cardiovasculaire (UMRS1180), Institut National de la Santé et de la Recherche Médicale (INSERM), Pidoux, Guillaume, Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV]Life Sciences [q-bio], Placenta, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, cAMP, medicine, Pharmacology (medical), phosphodiesterases, Protein kinase A, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, Original Research, Pharmacology, Syncytium, biology, lcsh:RM1-950, Phosphatases, Placentation, Trophoblast, Phosphodiesterase, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Cell biology, trophoblast fusion, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, lcsh:Therapeutics. Pharmacology, AKAPs, Immunology, biology.protein, Phosphorylation, protein kinase A, CREB1, Intracellular
Abstract: International audience; During human placentation, mononuclear cytotrophoblasts fuse to form multinucleated syncytia ensuring hormonal production and nutrient exchanges between the maternal and fetal circulation. Syncytial formation is essential for the maintenance of pregnancy and for fetal growth. The cAMP signaling pathway is the major route to trigger trophoblast fusion and its activation results in phosphorylation of specific intracellular target proteins, in transcription of fusogenic genes and assembly of macromolecular protein complexes constituting the fusogenic machinery at the plasma membrane. Specificity in cAMP signaling is ensured by generation of localized pools of cAMP controlled by cAMP phosphodiesterases (PDEs) and by discrete spatial and temporal activation of protein kinase A (PKA) in supramolecular signaling clusters inside the cell organized by A-kinase-anchoring proteins (AKAPs) and by organization of signal termination by protein phosphatases (PPs). Here we present original observations on the available components of the cAMP signaling pathway in the human placenta including PKA, PDE, and PP isoforms as well as AKAPs. We continue to discuss the current knowledge of the spatiotemporal regulation of cAMP signaling triggering trophoblast fusion.
Published: 2015

41. Anchored PKA as a gatekeeper for gap junctions

Author: Kjetil Taskén, Guillaume Pidoux, Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oslo (UiO), Oslo University Hospital [Oslo], and Pidoux, Guillaume
Subjects: A-kinase-anchoring protein, Cell type, Cell fusion, Chemistry, [SDV]Life Sciences [q-bio], Gap junction, Connexin, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Mini-Review, Bioinformatics, Cell biology, ezrin, Cx43, [SDV] Life Sciences [q-bio], gap junction, Ezrin, cAMP, cardiovascular system, Phosphorylation, PKA, sense organs, General Agricultural and Biological Sciences, Protein kinase A, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract: International audience; Anchored protein kinase A (PKA) bound to A Kinase Anchoring Protein (AKAP) mediates effects of localized increases in cAMP in defined subcellular microdomains and retains the specificity in cAMP-PKA signaling to distinct extracellular stimuli. Gap junctions are pores between adjacent cells constituted by connexin proteins that provide means of communication and transfer of small molecules. While the PKA signaling is known to promote human trophoblast cell fusion, the gap junction communication through connexin 43 (Cx43) is a prerequisite for this process. We recently demonstrated that trophoblast fusion is regulated by ezrin, a known AKAP, which binds to Cx43 and delivers PKA in the vicinity gap junctions. We found that disruption of the ezrin-Cx43 interaction abolished PKA-dependent phosphorylation of Cx43 as well as gap junction communication and subsequently cell fusion. We propose that the PKA-ezrin-Cx43 macromolecular complex regulating gap junction communication constitutes a general mechanism to control opening of Cx43 gap junctions by phosphorylation in response to cAMP signaling in various cell types.
Published: 2015

42. Formaldehyde Crosses the Human Placenta and Affects Human Trophoblast Differentiation and Hormonal Functions

Author: Pidoux, Guillaume, Gerbaud, Pascale, Guibourdenche, Jean, Therond, Patrice, Ferreira, Fatima, Simasotchi, Christelle, Evain-Brion, Danièle, Gil, Sophie, Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Pharmacie, Université Paris-Sud - Paris 11 (UP11), Fondation PremUp, Lipides membranaires et régulation fonctionnelle du coeur et des vaisseaux, Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, and Pidoux, Guillaume
Subjects: Adult, Amino Acid Transport System ASC, [SDV]Life Sciences [q-bio], lcsh:Medicine, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Minor Histocompatibility Antigens, Pregnancy, Formaldehyde, Humans, Placental Circulation, lcsh:Science, Maternal-Fetal Exchange, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Cells, Cultured, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, lcsh:R, Cell Differentiation, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Trophoblasts, [SDV] Life Sciences [q-bio], [SDV.TOX] Life Sciences [q-bio]/Toxicology, Oxidative Stress, [SDV.TOX]Life Sciences [q-bio]/Toxicology, embryonic structures, lcsh:Q, Female, Placental Hormones, Research Article
Abstract: International audience; The chorionic villus of the human placenta is the source of specific endocrine functions and nutrient exchanges. These activities are ensured by the syncytiotrophobast (ST), which bathes in maternal blood. The ST arises and regenerates throughout pregnancy by fusion of underlying cytotrophoblasts (CT). Any anomaly of ST formation or regeneration can affect pregnancy outcome and fetal growth. Because of its direct interaction with maternal blood, the ST is sensitive to drugs, pollutants and xenohormones. Ex vivo assays of perfused cotyledon show that formaldehyde, a common pollutant present in furniture, paint and plastics, can accumulate in the human placenta and cross to the fetal compartment. By means of RT-qPCR, immunoblot and immunocytochemistry experiments, we demonstrate in vitro that formaldehyde exerts endocrine toxicity on human trophoblasts, including a decrease in the production of protein hormones of pregnancy. In addition, formaldehyde exposure triggered human trophoblast fusion by upregulating syncitin-1 receptor expression (ASC-type amino-acid transporter 2: ASCT2). Moreover, we show that formaldehyde-exposed trophoblasts present an altered redox status associated with oxidative stress, and an increase in ASCT2 expression intended to compensate for this stress. Finally, we demonstrate that the adverse effects of formaldehyde on trophoblast differentiation and fusion are reversed by N-acetyl-L-cysteine (Nac), an antioxidant.
Published: 2015

43. Primary Bovine Extra-Embryonic Cultured Cells: A New Resource for the Study of In Vivo Peri-Implanting Phenotypes and Mesoderm Formation

Author: Thierry Fournier, Danièle Evain-Brion, Isabelle Hue, Séverine A. Degrelle, Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA)-Institut National Agronomique Paris-Grignon (INA P-G), La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), PremUp Foundation, Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Sorbonne Universités-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by PremUp foundation (S.A.D. post-doctoral fellowship), INRA Department programs ACI PHASE 2008, 2009, AIP AGROBI and EMBIC European network of excellence headed at INRA by O. Sandra., École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), DEGRELLE, Séverine, École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Fondation PremUp, This work was supported by the PremUp foundation (S.A.D. post‐doctoral fellowship), INRA Department programs ACI PHASE 2008, 2009, and AIP AGROBI, and the EMBIC European network of excellence at INRA headed by O. Sandra, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: bovin, lcsh:Medicine, Ectoderm, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Mesoderm, 0302 clinical medicine, Biologie de la reproduction, Embryonic disc, Cluster Analysis, lcsh:Science, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Cells, Cultured, développement de l'embryon, ComputingMilieux_MISCELLANEOUS, Genetics, Reproductive Biology, 0303 health sciences, culture cellulaire, 030219 obstetrics & reproductive medicine, Multidisciplinary, Biologie du développement, Gene Expression Regulation, Developmental, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Development Biology, 3. Good health, Cell biology, phénotype, Phenotype, medicine.anatomical_structure, embryonic structures, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Endoderm, Research Article, Cell type, Primary Cell Culture, mésoderme, Embryonic Development, Biology, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Animals, Embryo Implantation, phenopytes, extra-embryonic cell types, in vivo, micro-dissection, in vitro, mesoderm, crinoline, 030304 developmental biology, Gene Expression Profiling, lcsh:R, Embryogenesis, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Embryonic stem cell, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Mesoderm formation, lcsh:Q, Cattle, Transcriptome
Abstract: International audience; In addition to nourishing the embryo, extra-embryonic tissues (EETs) contribute to early em-bryonic patterning, primitive hematopoiesis, and fetal health. These tissues are of major importance for human medicine, as well as for efforts to improve livestock efficiency, but they remain incompletely understood. In bovines, EETs are accessible easily, in large amounts, and prior to implantation. We took advantage of this system to describe, in vitro and in vivo, the cell types present in bovine EETs at Day 18 of development. Specifically, we characterized the gene expression patterns and phenotypes of bovine extra-embryonic ectoderm (or trophoblast; bTC), endoderm (bXEC), and mesoderm (bXMC) cells in culture and compared them to their respective in vivo micro-dissected cells. After a week of culture, certain characteristics (e.g., gene expression) of the in vitro cells were altered with respect to the in vivo cells, but we were able to identify "cores" of cell-type-specific (and substrate-independent) genes that were shared between in vitro and in vivo samples. In addition, many cellular phenotypes were cell-type-specific with regard to extracellular adhesion. We evaluated the ability of individual bXMCs to migrate and spread on micro-patterns, and observed that they easily adapted to diverse environments, similar to in vivo EE mesoderm cells, which encounter different EE epithelia to form chorion, yolk sac, and allantois. With these tissue interactions , different functions arose that were detected in silico and corroborated in vivo at D21-D25. Moreover, analysis of bXMCs allowed us to identify the EE cell ring surrounding the embryonic disc (ED) at D14-15 as mesoderm cells, which had been hypothesized but not shown prior to this study. We envision these data will serve as a major resource for the future in the analysis of peri-implanting phenotypes in response to the maternal metabolism and contribute to subsequent studies of placental/fetal development in eutherians.
Published: 2015

44. Specific detection of type II human chorionic gonadotropin beta subunit produced by trophoblastic and neoplastic cells

Author: A. Nordor, F. Troalen, L. Aldaz-Carroll, Virginie Dangles-Marie, Thierry Fournier, Melanie Cocquebert, A.-M. Hersant, Alain Pecking, B. Guery, Dominique Bellet, Sophie Richon, D. Stevens, Jean Guibourdenche, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Centre de recherche de l'Institut Curie [Paris], Institut Curie [Paris], Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Institut Gustave Roussy (IGR), Génétique (Biologie pathologie), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpital René HUGUENIN (Saint-Cloud), Hôpital Renée Sabran [CHU - HCL], Hospices Civils de Lyon (HCL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and ORANGE, Colette
Subjects: [SDV]Life Sciences [q-bio], Clinical Biochemistry, Biochemistry, Human chorionic gonadotropin, 0302 clinical medicine, Pregnancy, Neoplasms, Gene expression, Chorionic Gonadotropin, beta Subunit, Human, TRANSCRIPTION, reproductive and urinary physiology, Immunoassay, 0303 health sciences, General Medicine, Immunohistochemistry, CANCER, 3. Good health, Trophoblasts, [SDV] Life Sciences [q-bio], PROGNOSTIC VALUE, medicine.anatomical_structure, 030220 oncology & carcinogenesis, embryonic structures, Female, hormones, hormone substitutes, and hormone antagonists, EXPRESSION, endocrine system, GENES, medicine.drug_class, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Monoclonal antibody, 03 medical and health sciences, Syncytiotrophoblast, [SDV.CAN] Life Sciences [q-bio]/Cancer, Placenta, Cell Line, Tumor, medicine, Humans, ASSAYS, FAMILIAL HCG SYNDROME, 030304 developmental biology, Biochemistry, medical, Biochemistry (medical), Trophoblast, Molecular biology, EVOLUTION, ALPHA, MRNA Sequencing, Down Syndrome, MONOCLONAL-ANTIBODIES, Gonadotropins
Abstract: International audience; Background: The sequence of the beta-subunit of human chorionic gonadotropin (hCG beta varies depending on whether hCG beta is encoded by type I or type II genes. Type II genes are upregulated in trophoblast and cancer but hCG beta can be detected in the serum of nonpregnant women and healthy individuals. We aimed to determine whether monoclonal antibody (mAb) FBT11-II specifically detects hCG beta encoded by type II genes (type II hCG beta). Methods: Competitive inhibition assays with synthetic peptides, immunocytochemical and immunohistochemical studies, type II hCG beta dosing immunoassays and sequencing of CGB genes were performed. Results: Competitive inhibition assays determined that mAb FBT11-II recognizes the type II hCG beta derived peptide. CGB mRNA sequencing of JEG-3 (trophoblastic) and 124 (bladder) cell lines confirmed that JEG-3 expresses type II genes while T24 expresses exclusively type I. FBT11-II only recognizes JEG-expressed hCG beta. Placenta immunohistochemical studies confirmed that type II hCG beta expression is restricted to the syncytiotrophoblast. Immunoassays detected type II hCG beta in serum of patients with either nontrophoblastic cancers or fetal Down syndrome. Conclusion: Type II gene expression can be detected using FBT11-II. This specific recognition could improve the clinical usefulness of assays aimed at either managing aggressive tumors or screening for Down syndrome.
Published: 2015

45. Transcriptome analysis of primary bovine extra-embryonic cultured cells

Author: Séverine A. Degrelle, Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), PremUp Foundation, Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the PremUp foundation (S.A.D. post-doctoral fellowship), INRA Department programs ACI PHASE 2008,2009, and AIP AGROB, École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut National Agronomique Paris-Grignon (INA P-G), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Sorbonne Universités-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and DEGRELLE, Séverine
Subjects: Cell type, Mesoderm, lcsh:QH426-470, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, Biochemistry, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Data in Brief, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Genetics, medicine, 030304 developmental biology, 0303 health sciences, 030219 obstetrics & reproductive medicine, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Embryo, Embryonic stem cell, Cell biology, lcsh:Genetics, medicine.anatomical_structure, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Cell culture, Mesoderm formation, embryonic structures, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Molecular Medicine, Endoderm, Biotechnology
Abstract: The dataset described in this article pertains to the article by Hue et al. (2015) entitled "Primary bovine extra-embryonic cultured cells: A new resource for the study of in vivo peri-implanting phenotypes and mesoderm formation" [1]. In mammals, extra-embryonic tissues are essential to support not only embryo patterning but also embryo survival, especially in late implanting species. These tissues are composed of three cell types: trophoblast (bTCs), endoderm (bXECs) and mesoderm (bXMCs). Until now, it is unclear how these cells interact. In this study, we have established primary cell cultures of extra-embryonic tissues from bovine embryos collected at day-18 after artificial insemination. We used our homemade bovine 10K array (GPL7417) to analyze the gene expression profiles of these primary extra-embryonic cultured cells compared to the corresponding cells from in vivo micro-dissected embryos. Here, we described the experimental design, the isolation of bovine extra-embryonic cell types as well as the microarray expression analysis. The dataset has been deposited in Gene Expression Omnibus (GEO) (accession number GSE52967). Finally, these primary cell cultures were a powerful tool to start studying their cellular properties, and will further allow in vitro studies on cellular interactions among extra-embryonic tissues, and potentially between extra-embryonic vs embryonic tissues. (C) 2015 The Author. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Published: 2015

46. Pattern of secretion of pregnancy-associated plasma protein-A (PAPP-A) during pregnancies complicated by fetal aneuploidy, in vivo and in vitro

Author: Jean Guibourdenche, Vassilis Tsatsaris, Marie Claude Menet, Agnes Choiset, Houria Salhi, Marie Clémence Leguy, Stephanie Brun, Guillaume Pidoux, Sophie Gil, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Maternité Port-Royal [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), PremUp Foundation, Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), UFR Pharmacie [Santé] - Université Paris Cité (UFR Pharmacie UPCité), Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Paris - UFR Pharmacie [Santé] (UP UFR Pharmacie), Université de Paris (UP), Pidoux, Guillaume, and Université Paris Cité - UFR Pharmacie [Santé] (UPCité UFR Pharmacie)
Subjects: Trisomy 13 Syndrome, Pregnancy-associated plasma protein A, Placenta, [SDV]Life Sciences [q-bio], Aneuploidy, Chromosome Disorders, Trisomy, Placental dysfunction, Chorionic Gonadotropin, Cohort Studies, 0302 clinical medicine, Endocrinology, Pregnancy, Pregnancy-Associated Plasma Protein-A, Cells, Cultured, 0303 health sciences, Villous cytotrophoblast, [SDV.BDLR.RS] Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, 030219 obstetrics & reproductive medicine, Obstetrics and Gynecology, Gestational age, Trophoblasts, Fetal trisomy, [SDV] Life Sciences [q-bio], Pregnancy-associated placental protein-A, Fetal Diseases, medicine.anatomical_structure, Maternal serum, Female, Nuchal Translucency Measurement, medicine.medical_specialty, Gestational Age, [SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, 03 medical and health sciences, Internal medicine, medicine, Humans, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, 030304 developmental biology, Fetus, Chromosomes, Human, Pair 13, business.industry, Research, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, medicine.disease, Ultrasound scanning, Pregnancy Complications, Reproductive Medicine, Down Syndrome, Chromosomes, Human, Pair 18, business, Developmental Biology
Abstract: International audience; Background: Pregnancy-associated placental protein-A (PAPP-A) is a metalloprotease which circulates as an hetero-tetramer in maternal blood. Its maternal serum concentration in fetal trisomy 21 is decreased during the first trimester, so that PAPP-A is a useful screening biomarker. However, the regulation of PAPP-A placental secretion is unclear. We therefore investigated the secretion of PAPP-A in pregnancies complicated by fetal aneuploidies, both in vivo and in vitro.Methods: Maternal serum collected between 10 WG and 33 WG during 7014 normal pregnancies and 96 pregnancies complicated by fetal trisomy 21, 18, and 13 were assayed for PAPP-A using the Immulite 2000xpi system®. The pregnancies were monitored using ultrasound scanning, fetal karyotyping and placental analysis. Villous cytotrophoblasts were isolated from normal and trisomic placenta and cultured to investigate PAPP-A secretion in vitro (n=6).Results: An increased nuchal translucency during the first trimester is a common feature of many chromosomal defect but each aneuploidy has its own syndromic pattern of abnormalities detectable at the prenatal ultrasound scanning and confirmed at the fetal examination thereafter. PAPP-A levels rise throughout normal pregnancy whereas in trisomy 21, PAPP-A levels were significantly decreased, but only during the first trimester. PAPP-A levels were decreased in trisomy 13 and sharply in trisomy 18, whatever the gestational age. In vitro, PAPP-A secretion was decreased in aneuploidy, and associated with decreased hCG secretion in Trisomy 21 and 18. These biochemical profiles did not appear to be linked to any specific histological lesions affecting the placenta.Conclusions: These profiles may reflect different quantitative and qualitative placental dysfunctions in the context of these aneuploidies.
Published: 2014

47. Review: An overview of molecular events occurring in human trophoblast fusion

Author: Pascale Gerbaud, Guillaume Pidoux, Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Pidoux, Guillaume
Subjects: Cell signaling, [SDV]Life Sciences [q-bio], Placenta, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Cell Communication, Biology, Cell Fusion, 03 medical and health sciences, Membrane Lipids, 0302 clinical medicine, Pregnancy, medicine, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, ZO-1, 030304 developmental biology, 0303 health sciences, Syncytium, Syncytins, 030219 obstetrics & reproductive medicine, Cell fusion, Obstetrics and Gynecology, Placentation, Trophoblast, Membrane Proteins, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Cell biology, Trophoblasts, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Reproductive Medicine, Membrane protein, Human trophoblast, Connexin 43, embryonic structures, cAMP-PKA signaling, Cadherin, Connexin-43, Female, Cytotrophoblasts, Fusion mechanism, Developmental Biology
Abstract: International audience; During human placentation, mononuclear cytotrophoblasts fuse to form a multinucleated syncytia ensuring hormonal production and nutrient exchanges between the maternal and fetal circulation. Syncytia formation is essential for the maintenance of pregnancy and for fetal growth. The trophoblast cell fusion process first requires the acquisition of cell fusion properties, then cells set up plasma membrane protein macrocomplexes and fusogen machinery that trigger cellecell fusion. Numerous proteins have been shown to be directly involved in the initiation of trophoblast cell fusion. These proteins must expressed at the right time and in the right place to trigger cellecell fusion. In this review, we describe the role of certain fusogenic protein macrocomplexes that form the scaffold for the fusogen machinery underlying human trophoblastic-lipid mixing and merging of cell contents that lead to cell fusion in physiological conditions.
Published: 2014

48. Breast cancer during pregnancy : taxanes interactions with human trophoblast using ex vivo and in vitro approaches

Author: Berveiller, Paul, Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université René Descartes - Paris V, Danièle Evain-Brion, STAR, ABES, and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Paclitaxel, Placenta, Primary trophoblast cultures, Transporteurs de médicaments, [SDV.CAN]Life Sciences [q-bio]/Cancer, Docetaxel, Docétaxel, Taxanes, Grossesse, [SDV.CAN] Life Sciences [q-bio]/Cancer, Pregnancy, Drug transporters, Culture primaire de trophoblastes, Cancer
Abstract: The occurrence of breast cancer during pregnancy is a dramatic event reaching roughly 1/3000 to 1/10000 pregnancies, this type of cancer being the most frequent in pregnant women. Regarding therapeutic options, some anticancer agents may be used, especially taxanes (paclitaxel and docetaxel). If most of retrospective data appear to be reassuring, little is known regarding their transplacental transfer. Moreover, to our knowledge, potential effects of taxanes on human placenta, especially on placental transport function are unknown. Our aims were to 1) provide a transcriptional expression cartography of various placental drug transporters throughout pregnancy, using primary trophoblast culture model, 2) assess the comparative transplacental transfer of taxanes and their accumulation in cotyledons, using the perfused placental model, 3) assess potential effects of paclitaxel on human placenta, especially on drug transporter expression, not only using above-described models, but also cotyledons from pregnant-cancer patients treated with paclitaxel during pregnancy. Here, we finally provided an original transcriptional cartography of various drugs transporters in human normal placenta all along pregnancy. Moreover, we found a low and comparable transplacental transfer of paclitaxel and docetaxel that led to a moderate accumulation in cotyledons. Finally, we evidenced a significant effect of paclitaxel on human placenta, especially by modulating drug transporter expression., La survenue d’un cancer du sein découvert durant la grossesse est un événement dramatique compliquant entre 1/3000 et 1/10000 grossesses, ce qui en fait le cancer le plus fréquemment rencontré chez la femme enceinte. Sur le plan thérapeutique, certaines molécules anticancéreuses peuvent être utilisées, notamment les taxanes (paclitaxel et docétaxel). Si les études cliniques rétrospectives isolées semblent plutôt rassurantes, les données concernant leur passage transplacentaire sont encore fragmentaires. Quant à leurs effets sur le placenta humain et plus particulièrement sur la fonction de transport placentaire, ils sont pour l’heure inconnus. Nos objectifs étaient de 1) dresser une cartographie de l’expression génique physiologique des différents transporteurs placentaires de médicaments en utilisant un modèle de culture primaire trophoblastique, 2) d’apprécier le passage transplacentaire comparatif des taxanes et leur accumulation placentaire en utilisant le modèle du cotylédon perfusé, 3) d’étudier plus particulièrement les effets du paclitaxel sur le placenta humain et notamment sur l’expression des transporteurs de médicaments, en utilisant en plus des modèles mentionnés, les cotylédons de patientes ayant été traitées par paclitaxel durant leur grossesse. Nos études ont tout d’abord permis de dresser une cartographie originale de l’expression physiologique de plus de 80 transporteurs placentaires de médicaments, et ce comparativement entre le début et la fin de la gestation. De plus, nos expériences ont montré que le passage transplacentaire des taxanes était faible et comparable entre les deux molécules, et que celles-ci semblaient s’accumuler dans les cotylédons placentaires. Enfin, nous avons pu mettre en évidence un effet significatif du paclitaxel sur le placenta humain, notamment sur la modulation de certains transporteurs de médicaments.
Published: 2014

49. Mesenchymal Activin-A Overcomes Defective Human Trisomy 21 Trophoblast Fusion

Author: Danièle Evain-Brion, Jean-Louis Frendo, Niroshani Pathirage, Jean Guibourdenche, Jean Marc Costa, Pascale Gerbaud, Guillaume Pidoux, Josette Badet, Padma Murthi, Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), PremUp Foundation, Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Melbourne, The Royal Women's Hospital, Laboratoire CERBA, Laboratoire CERBA [Saint Ouen l'Aumône], Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Pidoux, Guillaume
Subjects: medicine.medical_specialty, Placenta, Cellular differentiation, [SDV]Life Sciences [q-bio], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Cell Fusion, Mesoderm, 03 medical and health sciences, Paracrine signalling, Fetus, 0302 clinical medicine, Endocrinology, Pregnancy, Transforming Growth Factor beta, Internal medicine, Paracrine Communication, medicine, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, Cells, Cultured, reproductive and urinary physiology, 030304 developmental biology, 0303 health sciences, 030219 obstetrics & reproductive medicine, Cell fusion, Cytotrophoblast, biology, Mesenchymal stem cell, Trophoblast, Cell Differentiation, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Activins, Trophoblasts, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, embryonic structures, biology.protein, Cytokines, Female, Cytotrophoblasts, Down Syndrome, Follistatin
Abstract: International audience; Placental development is markedly abnormal in trisomy 21 (T21) pregnancies. We hypothesized that abnormal paracrine cross talk between the fetal mesenchymal core and the trophoblast might be involved in the defect of syncytiotrophoblast formation and function. In a large series of primary cultured human cytotrophoblasts isolated from second-trimester control (n = 44) and T21 placentae (n = 71), abnormal trophoblast fusion and differentiation was observed in more than 90% of T21 cases. We then isolated and cultured villous mesenchymal cells from control (n = 10) and T21 placentae (n = 8) and confirmed their fetal origin. Conditioned medium of control mesenchymal cells overcame the abnormal trophoblast fusion of T21 cytotrophoblasts by activating the TGFβ signaling pathway, as shown by the phosphospecific protein microarray analysis and the use of TGFβ signaling pathway antagonists. Using protein arrays, we further analyzed the cytokines present in the conditioned medium from control and T21 mesenchymal cells. Activin-A was identified as strongly secreted by cells from both sources, but at a significantly (P < 0.01) lower level in the case of T21 mesenchymal cells. Recombinant activin-A stimulated T21 trophoblast fusion. Blocking activin-A antibody inhibited the fusion induced by conditioned medium and exogenous activin-A. Furthermore, follistatin, an activin-A binding protein largely secreted by T21 mesenchymal cells, inhibited the conditioned medium fusogenic activity. These results show that the defective trophoblast fusion and differentiation associated with T21 can be overcome in vitro and reveal the key role of the fetal mesenchymal core in human trophoblast differentiation.
Published: 2011

50. Emergence and Dissemination of Extended‐Spectrum β‐Lactamase–Producing Escherichia coli in the Community: Lessons from the Study of a Remote and Controlled Population

Author: Cécile Angebault, François Rousset, H. Jacquier, Magaly Renard, Olivier Clermont, David Skurnik, Assiya El Mniai, Etienne Ruppé, Loïc Epelboin, Régis Marc Bettinger, Mathilde Lescat, Anaelle Da Costa, Claire Dupont, Erick Denamur, Paul-Louis Woerther, Antoine Andremont, Félix Djossou, Guillaume Arlet, Didier Guillemot, Hôpital Bichat, Assistance Publique - Hôpitaux de Paris, Emergence de la résistance bactérienne in vivo (EA3964), Université Paris Diderot - Paris 7 (UPD7), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Genomic Research Laboratory [Geneva, Switzerland], Geneva University Hospital (HUG), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Pharmacoépidémiologie et maladies infectieuses (PhEMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC), Ecologie et Evolution des Microorganismes (EEM), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne et maladies tropicales, CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Rural Population, MESH: Escherichia coli/enzymology, [SDV]Life Sciences [q-bio], Antibiotics, Prevalence, Drug resistance, medicine.disease_cause, Plasmid, Risk Factors, MESH: Community-Acquired Infections/microbiology, Epidemiology, polycyclic compounds, Immunology and Allergy, Escherichia coli Infections, 0303 health sciences, education.field_of_study, Anti-Bacterial Agents, French Guiana, 3. Good health, Community-Acquired Infections, Infectious Diseases, MESH: beta-Lactamases/biosynthesis, MESH: Escherichia coli Infections/microbiology, Carrier State, Female, Plasmids, Adult, medicine.medical_specialty, medicine.drug_class, Population, MESH: Escherichia coli/isolation & purification, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, beta-Lactam Resistance, beta-Lactamases, Microbiology, 03 medical and health sciences, Escherichia coli, medicine, Humans, education, 030304 developmental biology, 030306 microbiology, Indians, South American, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, Drug Utilization, MESH: beta-Lactam Resistance, MESH: Carrier State/microbiology, Carriage, Genes, Bacterial, bacteria, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Intestinal carriage is a key factor in extended-spectrum beta-lactamase (ESBL) infection epidemiology but is difficult to study in open communities. To overcome this problem, we studied a highly stable group of Amerindians for whom we reported an ESBL carriage prevalence of 3.2% in 2001. Methods In 2006, ESBL carriage was assessed among 163 healthy volunteer adults. ESBL isolates were identified, and their molecular resistance mechanisms were characterized. Antibiotic use in the year before sampling and the epidemiological characteristics of the population were analyzed. Results were compared to those obtained in 2001. Results In 2006, the ESBL carriage prevalence, exclusively comprising Escherichia coli, was 8.0%. It mainly consisted of CTX-M-type ESBL. The strains and plasmids carrying ESBL were heterogeneous, but 1 CTX-M-2-producing strain was found in 4.3% of the subjects analyzed. No individual risk factor was identified. However, overall antibiotic use had almost doubled since 2001. A 3-fold increase was noted for beta-lactams. Conclusions In this population, the frequency of ESBL increased with time because of the appearance of CTX-M ESBL, mimicking what occurs in the developed world. This resulted from the probable repeated introduction of new strains and plasmids and from interindividual dissemination. During the same period, antibiotic use substantially increased.
Published: 2010

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