| Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice. Auteur(s) : Hao, Chunxiang Gély-Pernot, Aurore Kervarrec, Christine Boudjema, Melissa Becker, Emmanuelle Khil, Pavel Tevosian, Sergei Jégou, Bernard Auteurs secondaires : Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - 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 ) Genetics and Biochemistry Branch ; National Institute of Health (NIH) - National Institute of Diabetes, Digestive and Kidney Diseases University of Florida [Gainesville] École des Hautes Études en Santé Publique [EHESP] (EHESP) Éditeur(s) : HAL CCSD Oxford University Press Résumé : International audience The epigenetic events imposed during germline reprogramming and affected by harmful exposure can be inherited and transferred to subsequent generations via gametes inheritance. In this study, we examine the transgenerational effects promoted by widely used herbicide atrazine (ATZ). We exposed pregnant outbred CD1 female mice and the male progeny was crossed for three generations with untreated females. We demonstrate here that exposure to ATZ affects meiosis, spermiogenesis and reduces the spermatozoa number in the third generation (F3) male mice. We suggest that changes in testis cell types originate from modified transcriptional network in undifferentiated spermatogonia. Importantly, exposure to ATZ dramatically increases the number of transcripts with novel transcription initiation sites, spliced variants and alternative polyadenylation sites. We found the global decrease in H3K4me3 occupancy in the third generation males. The regions with altered H3K4me3 occupancy in F3 ATZ-derived males correspond to altered H3K4me3 occupancy of F1 generation and 74% of changed peaks in F3 generation are associated with enhancers. The regions with altered H3K4me3 occupancy are enriched in SP family and WT1 transcription factor binding sites. Our data suggest that the embryonic exposure to ATZ affects the development and the changes induced by ATZ are transferred up to three generations. ISSN: 0305-1048 hal-01477213 https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477213 DOI : 10.1093/nar/gkw840 PUBMED : 27655631 | Partager
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