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9. List of contributors

Author

Agarwaal, Viplove, primary, Annacondia, Maria Luz, additional, Baruah, Kartik, additional, Basu, Amitava, additional, Ben Maamar, Millissia, additional, Bossier, Peter, additional, Casati, Lavinia, additional, Cavalieri, Vincenzo, additional, Celotti, Fabio, additional, Champagne, Frances A., additional, D'Cruz, Shereen Cynthia, additional, Diaz, Ruben, additional, Dwivedi, Ambey Prasad, additional, Fang, Lingzhao, additional, Freeman, Dana M., additional, Ge, Zhao-Jia, additional, Ho, Dao H., additional, Jiménez-Chillarón, Josep C., additional, Khosla, Sanjeev, additional, Legoff, Louis, additional, Lerin, Carles, additional, Li, Cong-Jun, additional, Lin, Shudai, additional, Liu, George E., additional, Martinez, German, additional, Mashoodh, Rahia, additional, Meyer-Ficca, Mirella L., additional, Meyer, Ralph G., additional, Mukherjee, Krishnendu, additional, Nilsson, Eric, additional, Norouzitallab, Parisa, additional, Nowak, Felicia V., additional, Palacios-Marin, Ivonne, additional, Rajeev, Ramisetti, additional, Ramon-Krauel, Marta, additional, Ribo, Silvia, additional, Riddle, Nicole C., additional, Schoelz, John M., additional, Sijbrands, Eric J.G., additional, Sinha, Anunay, additional, Skinner, Michael K., additional, Slyvka, Yuriy, additional, Smagulova, Fatima, additional, Spinelli, Giovanni, additional, Stuppia, Liborio, additional, Sun, Qing-Yuan, additional, Tevosian, Sergei, additional, Thamban, Thushara, additional, Tollefsbol, Trygve O., additional, Uller, Tobias, additional, Vanrompay, Daisy, additional, Varriale, Annalisa, additional, Vilcinskas, Andreas, additional, and Wang, Zhibin, additional

Published
2019
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15. Epigenome-wide association study of systemic effects of obesity susceptibility in human twins.

Author

Duncan, Glen E., Avery, Ally, Ben Maamar, Millissia, Nilsson, Eric E., Beck, Daniel, and Skinner, Michael K.

Subjects
OBESITY, DNA analysis, DNA methylation, PREVENTIVE medicine, DISEASE management
Abstract

The current study was designed to use an epigenome-wide association approach (EWAS) to identify potential systemic DNA methylation alterations that are associated with obesity using 22 discordant twin pairs. Buccal cells (from a cheek swab) were used as a non-obesity relevant purified marker cell for the epigenetic analysis. Analysis of differential DNA methylation regions (DMRs) was used to identify epigenetic associations with metabolic and dietary measures related to obesity with discordant twins. An edgeR analysis provided a DMR signature with p < 1e-04, but statistical significance was reduced due to low sample size and known multiple origins of obesity. A weighted gene coexpression network analysis (WGCNA) was performed and identified modules (p < 0.005) of epigenetic sites that correlated with different metabolic and dietary measures. The DMR and WGCNA epigenetic sites were near genes (e.g., CIDEC, SPP1, ZFPG9, and POMC) with previously identified obesity associated pathways (e.g., metabolism, cholesterol, and fat digestion). Observations demonstrate the feasibility of identifying systemic epigenetic biomarkers for obesity, which can be further investigated for clinical relevance in future research with larger sample sizes. The availability of a systemic epigenetic biomarker for obesity susceptibility may facilitate preventative medicine and clinical management of the disease early in life. KEY HIGHLIGHTS Analysis of differential DNA methylation regions (DMRs) was used to identify epigenetic associations with metabolic and dietary measures related to obesity with discordant twins. A weighted genome coexpression network analysis (WGCNA) was performed and identified modules of epigenetic sites that correlated with different metabolic and dietary measures. Observations demonstrate the feasibility of identifying systemic epigenetic biomarkers for obesity, which can be further investigated for clinical relevance in future research with larger sample sizes. The availability of a systemic epigenetic biomarker for obesity susceptibility may facilitate preventative medicine and clinical management of the disease early in life. [ABSTRACT FROM AUTHOR]

Published
2023
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32. Ibuprofen impacts germ cells in the human fetal ovary

Author

Leverrier-Penna, S., Mitchell, R.T., Emmanuelle, Becker, Ben Maamar, Millissia, Lavoue, Vincent, Kristensen, D.M., Jégou, Bernard, Dejucq-Rainsford, Nathalie, Mazaud-Guittot, Séverine, Mazaud-Guittot, Séverine, Antalgiques et différenciation ovarienne fœtale chez l'Homme - - ACETAMINOV2015 - ANR-15-CE34-0001 - AAPG2015 - VALID, 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 ), University of Edinburgh, Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Agence nationale de sécurité du médicament (# 2014S032), ANR-15-CE34-0001,ACETAMINOV,Antalgiques et différenciation ovarienne fœtale chez l'Homme(2015), and 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 )

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, ComputingMilieux_MISCELLANEOUS, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology
Abstract

International audience

Published
2017

33. Alterations in sperm DNA methylation, non-coding RNA expression, and histone retention mediate vinclozolin-induced epigenetic transgenerational inheritance of disease

Author

Ben Maamar, Millissia, primary, Sadler-Riggleman, Ingrid, additional, Beck, Daniel, additional, McBirney, Margaux, additional, Nilsson, Eric, additional, Klukovich, Rachel, additional, Xie, Yeming, additional, Tang, Chong, additional, Yan, Wei, additional, and Skinner, Michael K, additional

Published
2018
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35. Ibuprofen results in alterations of human fetal testis development

Author

Ben Maamar, Millissia, Lesné, Laurianne, Hennig, Kristin, Desdoits-Lethimonier, Christele, Kilcoyne, Karen R., Coiffec, Isabelle, Rolland, Antoine D., Chevrier, Cécile, Kristensen, David Møbjerg, Lavoue, Vincent, Antignac, Jean-Philippe, le Bizec, Bruno, Dejucq-Rainsford, Nathalie, Mitchell, Rod T., Mazaud-Guittot, Séverine, Jégou, Bernard, Ben Maamar, Millissia, Lesné, Laurianne, Hennig, Kristin, Desdoits-Lethimonier, Christele, Kilcoyne, Karen R., Coiffec, Isabelle, Rolland, Antoine D., Chevrier, Cécile, Kristensen, David Møbjerg, Lavoue, Vincent, Antignac, Jean-Philippe, le Bizec, Bruno, Dejucq-Rainsford, Nathalie, Mitchell, Rod T., Mazaud-Guittot, Séverine, and Jégou, Bernard

Published
2017

36. Dynamics of the transcriptional landscape during human fetal testis development

Author

Lecluze, Estelle, Rolland, Antoine D., Ben Maamar, Millissia, Coiffec, I., Filis, P., Fowler, P.A., Mazaud-Guittot, Séverine, Jégou, Bernard, Chalmel, Frédéric, Mazaud-Guittot, Séverine, 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 ), Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, and 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 )

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, ComputingMilieux_MISCELLANEOUS, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology
Abstract

International audience

Published
2016

39. Ibuprofen results in alterations of human fetal testis development

Author

Ben Maamar, Millissia, primary, Lesné, Laurianne, additional, Hennig, Kristin, additional, Desdoits-Lethimonier, Christèle, additional, Kilcoyne, Karen R., additional, Coiffec, Isabelle, additional, Rolland, Antoine D., additional, Chevrier, Cécile, additional, Kristensen, David M., additional, Lavoué, Vincent, additional, Antignac, Jean-Philippe, additional, Le Bizec, Bruno, additional, Dejucq-Rainsford, Nathalie, additional, Mitchell, Rod T., additional, Mazaud-Guittot, Séverine, additional, and Jégou, Bernard, additional

Published
2017
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40. Endocrine disruptive effects of ibuprofen on the human testis from fetal life to adulthood

Author

Ben Maamar, Millissia, Desdoits-Lethimonier, Christele, Lesné, Laurianne, Rolland, Antoine D., Coiffec, Isabelle, Kristensen, D.M., Lavoue, Vincent, Dejucq-Rainsford, Nathalie, Mazaud-Guittot, Séverine, Jégou, Bernard, 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 ), Novo Nordisk Foundation Center for Protein Research (CPR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM, AAP-2012–037), Mazaud-Guittot, Séverine, 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 ), and University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2015

41. Ibuprofen targets several cell types in the human fetal testis

Author

Ben Maamar, Millissia, Lesne, Laurianne, Rolland, Antoine D., Coiffec, I., Desdoits-Lethimonier, Christele, Kristensen, D.M., Lavoue, Vincent, Dejucq-Rainsford, Nathalie, Mazaud-Guittot, Séverine, Jégou, Bernard, Mazaud-Guittot, Séverine, Institut de recherche en santé, environnement et travail (Irset), 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 ), Novo Nordisk Foundation Center for Protein Research (CPR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM, AAP-2012–037), 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 ), and University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, ComputingMilieux_MISCELLANEOUS, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology
Abstract

National audience

Published
2015

42. An Investigation of the Endocrine-Disruptive Effects of Bisphenol A in Human and Rat Fetal Testes

Author

Ben Maamar, Millissia, Lesné, Laurianne, Desdoits-Lethimonier, Christèle, Coiffec, Isabelle, Lassurguère, Julie, Lavoué, Vincent, Deceuninck, Yoann, Antignac, Jean-Philippe, Le Bizec, Bruno, Perdu, Elisabeth, Zalko, Daniel, Pineau, Charles, Chevrier, Cécile, Dejucq-Rainsford, Nathalie, Mazaud-Guittot, Séverine, Jégou, Bernard, Institut de recherche en santé, environnement et travail (Irset), 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), Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Santé Environnement Travail et Génie Sanitaire (DSETGS), Inserm (Institut National de la Sante et de la Recherche Medicale), Ministere de l'Enseignement Superieur et de la Recherche, EHESP - School of Public Health, Agence Nationale de Securite Sanitaire de l'Alimentation, de l'Environnement et du Travail (ANSES) [EST-2010/2/046, EST-2012/2/171], Agence Nationale de la Recherche (ANR) [ANR-13-CESA-0012-03], Ministere de l'Ecologie, du Developpement Durable et de l'Energie (MEDDE) [13-MRES-PNRPE-5-CUS-047], ANR-13-CESA-0012,NEWPLAST,Contribution à l'évaluation de l'exposition de l'Homme aux substituts et dérivés du Bisphenol A et à la caractérisation du danger associé.(2013), 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 ), Pôle de gynécologie, obstétrique et médecine de la reproduction[Rennes], CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, Laboratoire d'Etude des Résidus et Contaminants dans les Aliments, Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), 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 ), Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Jonchère, Laurent, and Contaminants et Environnements : Santé, Adaptabilité, Comportements et Usages - Contribution à l'évaluation de l'exposition de l'Homme aux substituts et dérivés du Bisphenol A et à la caractérisation du danger associé. - - NEWPLAST2013 - ANR-13-CESA-0012 - CESA - VALID

Subjects
Male, endocrine system, Pollutants, Production control, [SDV]Life Sciences [q-bio], Sertoli cells, lcsh:Medicine, Endocrine Disruptors, Rats, Sprague-Dawley, Phenols, Pregnancy, Testis, Animals, Humans, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Testosterone, Testes, Benzhydryl Compounds, Rats, Wistar, lcsh:Science, ComputingMilieux_MISCELLANEOUS, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Fetuses, Ethanol, urogenital system, lcsh:R, Correction, Rats, [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Female, lcsh:Q, hormones, hormone substitutes, and hormone antagonists, Research Article
Abstract

International audience; Few studies have been undertaken to assess the possible effects of bisphenol A (BPA) on the reproductive hormone balance in animals or humans with often contradictory results. We investigated possible direct endocrine disruption by BPA of the fetal testes of 2 rat strains (14.5–17.5 days post-coitum) and humans (8–12 gestational weeks) and under different culture conditions. BPA concentrations of 10-8M and 10-5M for 72h reduced testosterone production by the Sprague-Dawley fetal rat testes, while only 10-5M suppressed it in the Wistar strain. The suppressive effects at 10-5M were seen as early as 24h and 48h in both strains. BPA at 10-7-10-5M for 72h suppressed the levels of fetal rat Leydig cell insulin-like factor 3 (INSL3). BPA exposure at 10-8M, 10-7M, and 10-5M for 72h inhibited testosterone production in fetal human testes. For the lowest doses, the effects observed occurred only when no gonadotrophin was added to the culture media and were associated with a poorly preserved testicular morphology. We concluded that (i) BPA can display anti-androgenic effects both in rat and human fetal testes; (ii) it is essential to ascertain that the divergent effects of endocrine disruptors between species in vitro do not result from the culture conditions used, and/or the rodent strain selected; (iii) the optimization of each in vitro assay for a given species should be a major objective rather than the search of an hypothetical trans-species consensual model-system, as the organization of the testis is intrinsically different between mammalian species; (iv) due to the uncertainty existing on the internal exposure of the human fetal testis to BPA, and the insufficient number of epidemiological studies on the endocrine disruptive effects of BPA, caution should be taken in the extrapolation of our present results to the human reproductive health after fetal exposure to BPA.

Published
2015

43. Ibuprofen disrupts the endocrine function of the human adult testis

Author

Desdoits-Lethimonier, Christele, Lesne, Laurianne, Mazaud-Guittot, Séverine, Ben Maamar, Millissia, Kristensen, D.M., Bensalah, Karim, Platel, Christian, Dejucq-Rainsford, Nathalie, Jégou, Bernard, Mazaud-Guittot, Séverine, 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 ), Novo Nordisk Foundation Center for Protein Research (CPR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Pontchaillou [Rennes], 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 ), and University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, ComputingMilieux_MISCELLANEOUS, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology
Abstract

International audience

Published
2015

44. Histone-mediated transgenerational epigenetics

Author

Vincenzo Cavalieri, Giovanni Spinelli, Tollefsbol,Trygve O, Tollefsbol,Trygve O., Nilsson, Eric, Ben Maamar, Millissia, Skinner, Michael K., Ho, Dao H., Meyer-Ficca, Mirella L., Meyer, Ralph G., Ge, Zhao-Jia, Sun, Qing-Yuan, Mashoodh, Rahia, Champagne, Frances A., Freeman, Dana M., Wang, Zhibin, Cavalieri, Vincenzo, Spinelli, Giovanni, Schoelz, John M., Riddle, Nicole C., Legof, Loui, D’Cruz, Shereen Cynthia, Tevosian, Sergei, Smagulova, Fatima, Norouzitallab, Parisa, Baruah, Kartik, Bossier, Peter, Vanrompay, Daisy, Annacondia, Maria Luz, Martinez, German, Lin, Shudai, Fang, Lingzhao, Liu, George E., Li, Cong-Jun, Mukherjee, Krishnendu, Vilcinskas, Andrea, Uller, Tobia, Varriale, Annalisa, Casati, Lavinia, Celotti, Fabio, Stuppia, Liborio, Thamban, Thushara, Agarwaal, Viplove, Basu, Amitava, Rajeev, Ramisetti, Sinha, Anunay, Prasad Dwivedi, Ambey, Khosla, Sanjeev, Nowak, Felicia V., Slyvka, Yuriy, Ribo, Silvia, Ramon-Krauel, Marta, Palacios-Marin, Ivonne, Diaz, Ruben, Lerin, Carle, Jiménez-Chillaro´n, Josep C., Sijbrands, Eric J.G., Cavalieri Vincenzo, and Spinelli Giovanni

Subjects
Genetics, Histone, biology.protein, Inheritance (genetic algorithm), Nucleosome, Settore BIO/11 - Biologia Molecolare, Epigenetics, Histone-based epigenetic inheritanceHistone inheritance in diseaseHistone posttranslational modificationsHistone variantsNucleosome positioningPerpetuation of maternal histonesRetention of paternal nucleosomeTransgenerational transmission of environmental information, Biology, Genome, Phenotype, Germline, Chromatin
Abstract

Epigenetic mechanisms operate at the interface between the environment and genome, by converting the environmental stimuli to phenotypic responses through changes in the chromatin landscape, which ultimately affects gene expression in the absence of alterations in DNA sequence. In this scenario, transgenerational inheritance occurs when epigenetic variations induced by environmental stimuli are transmitted through the germ line to succeeding generations that had never experienced those stimuli. There is an ever-growing list of reports indicating that histones are fundamental players in these processes in a variety of organisms. In this chapter, we provide a perspective on histone-driven epigenetic mechanisms, such as histone posttranslational modifications, incorporation of histone variants, and nucleosome positioning, illustrating their interwoven hierarchies of activity and highlighting their roles in the transgenerational inheritance of genomic functions.

Published
2019

45. Genome-Wide Mapping of DNA Methylation 5mC by Methylated DNA Immunoprecipitation (MeDIP)-Sequencing.

Author

Ben Maamar M, Sadler-Riggleman I, Beck D, and Skinner MK

Subjects
Animals, Base Sequence, Chromosome Mapping, Cytidine immunology, DNA genetics, DNA immunology, DNA Methylation genetics, DNA Methylation immunology, Genome, Genome-Wide Association Study methods, High-Throughput Nucleotide Sequencing methods, Humans, Cytidine analogs & derivatives, Immunoprecipitation methods, Sequence Analysis, DNA methods
Abstract

Methylated DNA immunoprecipitation is a large scale purification technique. It enables the isolation of methylated DNA fragments for subsequent locus-specific or genome-wide analysis. Here we describe an immunoprecipitation protocol using a monoclonal mouse anti 5-methyl-cytidine antibody followed by next-generation sequencing (MeDIP-Seq).

Published
2021
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46. An investigation of the endocrine-disruptive effects of bisphenol a in human and rat fetal testes.

Author

Ben Maamar M, Lesné L, Desdoits-Lethimonier C, Coiffec I, Lassurguère J, Lavoué V, Deceuninck Y, Antignac JP, Le Bizec B, Perdu E, Zalko D, Pineau C, Chevrier C, Dejucq-Rainsford N, Mazaud-Guittot S, and Jégou B

Subjects
Animals, Female, Humans, Male, Pregnancy, Rats, Rats, Sprague-Dawley, Rats, Wistar, Testis embryology, Benzhydryl Compounds toxicity, Endocrine Disruptors toxicity, Phenols toxicity, Testis drug effects
Abstract

Few studies have been undertaken to assess the possible effects of bisphenol A (BPA) on the reproductive hormone balance in animals or humans with often contradictory results. We investigated possible direct endocrine disruption by BPA of the fetal testes of 2 rat strains (14.5-17.5 days post-coitum) and humans (8-12 gestational weeks) and under different culture conditions. BPA concentrations of 10(-8)M and 10(-5)M for 72 h reduced testosterone production by the Sprague-Dawley fetal rat testes, while only 10-5M suppressed it in the Wistar strain. The suppressive effects at 10-5M were seen as early as 24h and 48 h in both strains. BPA at 10(-7)-10(-5)M for 72 h suppressed the levels of fetal rat Leydig cell insulin-like factor 3 (INSL3). BPA exposure at 10(-8)M, 10(-7)M, and 10(-5)M for 72 h inhibited testosterone production in fetal human testes. For the lowest doses, the effects observed occurred only when no gonadotrophin was added to the culture media and were associated with a poorly preserved testicular morphology. We concluded that (i) BPA can display anti-androgenic effects both in rat and human fetal testes; (ii) it is essential to ascertain that the divergent effects of endocrine disruptors between species in vitro do not result from the culture conditions used, and/or the rodent strain selected; (iii) the optimization of each in vitro assay for a given species should be a major objective rather than the search of an hypothetical trans-species consensual model-system, as the organization of the testis is intrinsically different between mammalian species; (iv) due to the uncertainty existing on the internal exposure of the human fetal testis to BPA, and the insufficient number of epidemiological studies on the endocrine disruptive effects of BPA, caution should be taken in the extrapolation of our present results to the human reproductive health after fetal exposure to BPA.

Published
2015
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47. Paracetamol, aspirin, and indomethacin induce endocrine disturbances in the human fetal testis capable of interfering with testicular descent.

Author

Mazaud-Guittot S, Nicolas Nicolaz C, Desdoits-Lethimonier C, Coiffec I, Ben Maamar M, Balaguer P, Kristensen DM, Chevrier C, Lavoué V, Poulain P, Dejucq-Rainsford N, and Jégou B

Subjects
Abortion, Induced, Analgesics, Non-Narcotic adverse effects, Androgens metabolism, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Cryptorchidism pathology, Female, Fetus pathology, Humans, Male, Organ Culture Techniques, Pregnancy, Pregnancy Trimester, First, Testis abnormalities, Testis metabolism, Testosterone metabolism, Abnormalities, Drug-Induced etiology, Acetaminophen adverse effects, Aspirin adverse effects, Cryptorchidism chemically induced, Fetus drug effects, Indomethacin adverse effects
Abstract

Context: Masculinization depends on the fetal testis. Exposure of the human fetus during pregnancy to paracetamol and/or to other mild analgesics is associated with an increased risk of cryptorchidism., Objective: We aimed to determine whether mild analgesics disrupted the morphology and endocrine function of the human testis., Design: We used an in vitro system based on the culture of human fetal testes exposed or not to paracetamol, its metabolite N-(4-hydroxyphenyl)-arachidonoylethanolamide (AM404), aspirin, indomethacin, and ketoconazole at 10(-4) to 10(-7) M., Setting: The study was conducted at the University of Rennes I., Patients/participants: Human fetal testes were from pregnant women after induced abortion, between 7 and 12 weeks of gestation (GW)., Main Outcome Measures: Testosterone (RIA), anti-Müllerian hormone (ELISA), insulin-like factor 3 (RIA), and prostaglandin (PG) D2 and PGE2 (ELISA) were assayed in the medium. Testicular cells were counted using histology and image analysis. The possible nuclear receptor-mediated activities of the analgesics were investigated using reporter cell lines expressing estrogen, androgen, and peroxisome proliferator-activated γ receptors., Results: Indomethacin and aspirin stimulated testosterone production, particularly by the younger testes (8-9 GW vs 10-12 GW). Paracetamol, AM404, and ketoconazole decreased insulin-like factor 3 levels. Aspirin stimulated whereas ketoconazole inhibited AMH production. PGE2 levels were inhibited by paracetamol and aspirin in the 7 to 12 GW testes and by indomethacin but only in 7 to 9.86 GW testes. The inhibitory trends seen for PGD2 were not statistically significant., Conclusions: Analgesics at concentrations relevant to human exposure cause endocrine disturbances in the fetal testis. We suggest that the fetal human testis displays slight critical age windows for sensitivity to direct exposure to aspirin, indomethacin, and paracetamol. The analgesic-induced inhibition of INSL3 may be the mechanism by which analgesics increase the risk of cryptorchidism. Greater caution is required concerning consumption of analgesics during pregnancy.

Published
2013
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