Gestational exposure to chlordecone promotes transgenerational changes in the murine reproductive system of males

Abstract Environmental factors can affect epigenetic events during germline reprogramming and impose distinctive transgenerational consequences onto the offspring. In this study, we examined the transgenerational effects of chlordecone (CD), an organochlorine insecticide with well-known estrogenic p...

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Autores principales: Aurore Gely-Pernot, Chunxiang Hao, Louis Legoff, Luc Multigner, Shereen Cynthia D’Cruz, Christine Kervarrec, Bernard Jégou, Sergei Tevosian, Fatima Smagulova
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Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/fd7c4c97e7ae40d68af8b0d27cb0ba8f
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spelling oai:doaj.org-article:fd7c4c97e7ae40d68af8b0d27cb0ba8f2021-12-02T15:08:01ZGestational exposure to chlordecone promotes transgenerational changes in the murine reproductive system of males10.1038/s41598-018-28670-w2045-2322https://doaj.org/article/fd7c4c97e7ae40d68af8b0d27cb0ba8f2018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-28670-whttps://doaj.org/toc/2045-2322Abstract Environmental factors can affect epigenetic events during germline reprogramming and impose distinctive transgenerational consequences onto the offspring. In this study, we examined the transgenerational effects of chlordecone (CD), an organochlorine insecticide with well-known estrogenic properties. We exposed pregnant mice to CD from embryonic day 6.5 to 15.5 and observed a reduction in spermatogonia (SG) numbers in F3, meiotic defects in spermatocytes and decrease in spermatozoa number in the first and third generation of male progeny. The RNA qRT-PCR expression analysis in F1 and transcriptomics analysis in F3 males using the whole testes revealed changes in the expression of genes associated with chromosome segregation, cell division and DNA repair. The expression of the master regulator of pluripotency, Pou5f1, decreased in foetal and increased in adult F1, but not in F3 adult testes. Analysis of histone H3K4me3 distribution revealed widespread changes in its occupancy in the genome of F1 and F3 generations. We established that 7.1% of altered epigenetic marks were conserved between F1 and F3 generations. The overlapping changes common to F1 and F3 include genes implicated in cell adhesion and transcription factor activities functions. Differential peaks observed in F1 males are significantly enriched in predicted ESR1 binding sites, some of which we confirmed to be functional. Our data demonstrate that CD-mediated impairment of reproductive functions could be transmitted to subsequent generations.Aurore Gely-PernotChunxiang HaoLouis LegoffLuc MultignerShereen Cynthia D’CruzChristine KervarrecBernard JégouSergei TevosianFatima SmagulovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-18 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Aurore Gely-Pernot
Chunxiang Hao
Louis Legoff
Luc Multigner
Shereen Cynthia D’Cruz
Christine Kervarrec
Bernard Jégou
Sergei Tevosian
Fatima Smagulova
Gestational exposure to chlordecone promotes transgenerational changes in the murine reproductive system of males
description Abstract Environmental factors can affect epigenetic events during germline reprogramming and impose distinctive transgenerational consequences onto the offspring. In this study, we examined the transgenerational effects of chlordecone (CD), an organochlorine insecticide with well-known estrogenic properties. We exposed pregnant mice to CD from embryonic day 6.5 to 15.5 and observed a reduction in spermatogonia (SG) numbers in F3, meiotic defects in spermatocytes and decrease in spermatozoa number in the first and third generation of male progeny. The RNA qRT-PCR expression analysis in F1 and transcriptomics analysis in F3 males using the whole testes revealed changes in the expression of genes associated with chromosome segregation, cell division and DNA repair. The expression of the master regulator of pluripotency, Pou5f1, decreased in foetal and increased in adult F1, but not in F3 adult testes. Analysis of histone H3K4me3 distribution revealed widespread changes in its occupancy in the genome of F1 and F3 generations. We established that 7.1% of altered epigenetic marks were conserved between F1 and F3 generations. The overlapping changes common to F1 and F3 include genes implicated in cell adhesion and transcription factor activities functions. Differential peaks observed in F1 males are significantly enriched in predicted ESR1 binding sites, some of which we confirmed to be functional. Our data demonstrate that CD-mediated impairment of reproductive functions could be transmitted to subsequent generations.
format article
author Aurore Gely-Pernot
Chunxiang Hao
Louis Legoff
Luc Multigner
Shereen Cynthia D’Cruz
Christine Kervarrec
Bernard Jégou
Sergei Tevosian
Fatima Smagulova
author_facet Aurore Gely-Pernot
Chunxiang Hao
Louis Legoff
Luc Multigner
Shereen Cynthia D’Cruz
Christine Kervarrec
Bernard Jégou
Sergei Tevosian
Fatima Smagulova
author_sort Aurore Gely-Pernot
title Gestational exposure to chlordecone promotes transgenerational changes in the murine reproductive system of males
title_short Gestational exposure to chlordecone promotes transgenerational changes in the murine reproductive system of males
title_full Gestational exposure to chlordecone promotes transgenerational changes in the murine reproductive system of males
title_fullStr Gestational exposure to chlordecone promotes transgenerational changes in the murine reproductive system of males
title_full_unstemmed Gestational exposure to chlordecone promotes transgenerational changes in the murine reproductive system of males
title_sort gestational exposure to chlordecone promotes transgenerational changes in the murine reproductive system of males
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/fd7c4c97e7ae40d68af8b0d27cb0ba8f
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