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1. TRIM28-dependent SUMOylation protects the adult ovary from activation of the testicular pathway

Author

Robin Lovell-Badge, Francis Poulat, Moïra Rossitto, Le Gallic L, Dagmar Wilhelm, Alain Pruvost, Brigitte Boizet-Bonhoure, Legras S, Mahmoud-Reza Rafiee, Florence Cammas, Migale R, Serge Nef, Yasmine Neirijnck, Anvi Laetitia Nguyen, Guillaume Bossis, Chris M Rands, Stéphanie Déjardin, Institut de génétique humaine (IGH), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Genève = University of Geneva (UNIGE), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The Francis Crick Institute [London], Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Génétique Moléculaire de Montpellier (IGMM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Melbourne, cammas, florence, and ANR-16-CE14-0020,SexMaintain,Rôle de TRIM28 dans le maintien de l'identité ovarienne et dans la détermination du sexe(2016)

Subjects
Male, Model organisms, endocrine system, Somatic cell, [SDV]Life Sciences [q-bio], SUMO protein, General Physics and Astronomy, Tripartite Motif-Containing Protein 28, Biology, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Testis, medicine, Animals, Ligase activity, Transcription factor, 030304 developmental biology, Mammals, 0303 health sciences, Sertoli Cells, Multidisciplinary, urogenital system, FOS: Clinical medicine, Stem Cells, Ovary, Transdifferentiation, Neurosciences, Sumoylation, General Chemistry, Tumour Biology, Sertoli cell, Embryonic stem cell, Chromatin, Cell biology, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Female, Genetics & Genomics, 030217 neurology & neurosurgery, Transcription Factors, Developmental Biology
Abstract

Summary Gonadal sexual fate in mammals is determined during embryonic development and must be actively maintained in adulthood. Therefore, gonadal sex-specific transcription factors are required to prevent transdifferentiation of gonadal somatic cells to the other sexual fate. Mouse genetic experiments have shown that oestrogen receptor signalling and the transcription factor FOXL2 protect ovarian granulosa cells from transdifferentiation into Sertoli cells, their testicular counterpart. However, the mechanism underlying this protective mechanism is unknown. Here, we show that one post-translational modification (i.e. SUMOylation catalysed by TRIM28) is sufficient to prevent female-to-male sex reversal of the mouse ovary after birth. We found that upon loss of TRIM28 SUMO-E3 ligase activity, ovarian granulosa cells transdifferentiate to Sertoli cells through an intermediate cell type different from gonadal embryonic progenitors. TRIM28 binds to chromatin close to the critical transcription factor FOXL2 to maintain the female pathway through SUMOylation of specific chromatin regions. Therefore, FOXL2 signalling might maintain the adult ovary cell fate via TRIM28-dependent SUMOylation. Improper SUMOylation of chromatin regions in granulosa cells might lead to female reproductive disorders and infertility, the incidence of which is currently increasing.

Published
2022
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2. Cucurbit[5]uril derivatives as oxygen carriers

Author

Gaspard Huber, Patrick Berthault, Anvi Laetitia Nguyen, Alain Pruvost, Elodie Barruet, Julie Rivollier, Marie-Pierre Heck, Benoît Prieur, Laboratoire Structure et Dynamique par Résonance Magnétique (LCF) (LSDRM), 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)-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), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire Interdisciplinaire sur l'Organisation Nanométrique et Supramoléculaire (LIONS), Service de Chimie Bio-Organique et de Marquage (SCBM), 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 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-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Service de Pharmacologie et d'Immunoanalyse (SPI), and Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
[CHIM.ORGA]Chemical Sciences/Organic chemistry, 010405 organic chemistry, Supramolecular chemistry, chemistry.chemical_element, [CHIM.MATE]Chemical Sciences/Material chemistry, General Chemistry, 010402 general chemistry, 01 natural sciences, Oxygen, supramolecular chemistry, cucurbituril, 0104 chemical sciences, 3. Good health, dissolved gas binding, chemistry, Cucurbituril, oxygen carrier, Polymer chemistry
Abstract

International audience; Cucurbit[n]urils are rigid cage-molecules of pumpkin-like shape, made of n-glycoluril units, able to bind mainly neutral molecules and cations. In this work, we investigate the binding of three cucurbit[5]uril derivatives with dioxygen O$_2$ and show that one of them, namely per-hydroxylated cucurbit[5]uril, (OH)$_{10}$CB[5], is able to significantly bind dioxygen gas at physiological temperature, even in the presence of sodium chloride at the concentration of injectable solution in blood. As cucurbit[n]urils studied up to now reveal low toxicity, per-hydroxylated cucurbit[5]uril appears as a promising precursor to design a host able to transport O$_2$ in a haemoglobin substitute solution.

Published
2019
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3. In the mouse, prostaglandin D2 signalling protects the endometrium against adenomyosis

Author

Francis Poulat, Alain Pruvost, Stephanie Dejardin, Nelly Pirot, Anvi Laetitia Nguyen, Pascal Philibert, Brigitte Boizet-Bonhoure, Florence Bernex, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), BioCampus (BCM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Embryology, mouse model, [SDV]Life Sciences [q-bio], Uterus, Vimentin, Biology, Lipocalin, Real-Time Polymerase Chain Reaction, Endometrium, Dinoprostone, Extracellular matrix, Andrology, Mice, 03 medical and health sciences, 0302 clinical medicine, Genetics, medicine, Animals, Adenomyosis, endometrium, Molecular Biology, 030304 developmental biology, prostaglandin E2, 0303 health sciences, 030219 obstetrics & reproductive medicine, Prostaglandin D2, [SDV.BA]Life Sciences [q-bio]/Animal biology, Myometrium, Obstetrics and Gynecology, Cell Biology, medicine.disease, Lipocalins, 3. Good health, Intramolecular Oxidoreductases, medicine.anatomical_structure, Reproductive Medicine, biology.protein, Female, Steroids, lipids (amino acids, peptides, and proteins), Myofibroblast, Signal Transduction, Developmental Biology
Abstract

Adenomyosis is characterised by epithelial gland and mesenchymal stroma invasion of the uterine myometrium. Adenomyosis is an oestrogen-dependent gynaecological disease in which a number of factors, such as inflammatory molecules, prostaglandins (PGs), angiogenic factors, cell proliferation and extracellular matrix remodelling proteins, also play a role as key disease mediators. In this study, we used mice lacking both lipocalin and hematopoietic-PG D synthase (L- and H-Pgds) genes in which PGD2 is not produced to elucidate PGD2 roles in the uterus. Gene expression studied by real-time PCR and hormone dosages performed by ELISA or liquid chromatography tandem mass spectroscopy in mouse uterus samples showed that components of the PGD2 signalling pathway, both PGDS and PGD2-receptors, are expressed in the mouse endometrium throughout the oestrus cycle with some differences among uterine compartments. We showed that PGE2 production and the steroidogenic pathway are dysregulated in the absence of PGD2. Histological analysis of L/H-Pgds−/− uteri, and immunohistochemistry and immunofluorescence analyses of proliferation (Ki67), endothelial cell (CD31), epithelial cell (pan-cytokeratin), myofibroblast (α-SMA) and mesenchymal cell (vimentin) markers, identify that 6-month-old L/H-Pgds−/− animals developed adenomyotic lesions, and that disease severity increased with age. In conclusion, this study suggests that the PGD2 pathway has major roles in the uterus by protecting the endometrium against adenomyosis development. Additional experiments, using for instance transcriptomic approaches, are necessary to fully determine the molecular mechanisms that lead to adenomyosis in L/H-Pgds−/− mice and to confirm whether this strain is an appropriate model for studying the human disease.

Published
2021
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4. Cucurbit[5]uril derivatives as oxygen carriers

Author

Huber, Gaspard, Berthault, Patrick, Anvi Laetitia Nguyen, Pruvost, Alain, Barruet, Elodie, Rivollier, Julie, Heck, Marie-Pierre, and Prieur, Benoît

Subjects
3. Good health
Abstract

Cucurbit[n]urils are rigid cage-molecules of pumpkin-like shape, made of n-glycoluril units, able to bind mainly neutral molecules and cations. In this work, we investigate the binding of three cucurbit[5]uril derivatives with dioxygen O2 and show that one of them, namely per-hydroxylated cucurbit[5]uril, (OH)10CB[5], is able to significantly bind dioxygen gas at physiological temperature, even in the presence of sodium chloride at the concentration of injectable solution in blood. As cucurbit[n]urils studied up to now reveal low toxicity, per-hydroxylated cucurbit[5]uril appears as a promising precursor to design a host able to transport O2 in a haemoglobin substitute solution.

5. Cucurbit[5]uril derivatives as oxygen carriers

Author

Huber, Gaspard, Berthault, Patrick, Anvi Laetitia Nguyen, Pruvost, Alain, Barruet, Elodie, Rivollier, Julie, Heck, Marie-Pierre, and Prieur, Benoît

Subjects
3. Good health
Abstract

Cucurbit[n]urils are rigid cage-molecules of pumpkin-like shape, made of n-glycoluril units, able to bind mainly neutral molecules and cations. In this work, we investigate the binding of three cucurbit[5]uril derivatives with dioxygen O2 and show that one of them, namely per-hydroxylated cucurbit[5]uril, (OH)10CB[5], is able to significantly bind dioxygen gas at physiological temperature, even in the presence of sodium chloride at the concentration of injectable solution in blood. As cucurbit[n]urils studied up to now reveal low toxicity, per-hydroxylated cucurbit[5]uril appears as a promising precursor to design a host able to transport O2 in a haemoglobin substitute solution.

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