title: The epigenetic processes of meiosis in male mice are broadly affected by the widely used herbicide atrazine.
abstract: BACKGROUND
  Environmental factors such as pesticides can cause phenotypic changes in various organisms, including mammals. We studied the effects of the widely used herbicide atrazine (ATZ) on meiosis, a key step of gametogenesis, in male mice.
  
  
  METHODS
  Gene expression pattern was analysed by Gene-Chip array. Genome-wide mapping of H3K4me3 marks distribution was done by ChIP-sequencing of testis tissue using Illumina technologies. RT-qPCR was used to validate differentially expressed genes or differential peaks.
  
  
  RESULTS
  We demonstrate that exposure to ATZ reduces testosterone levels and the number of spermatozoa in the epididymis and delays meiosis. Using Gene-Chip and ChIP-Seq analysis of H3K4me3 marks, we found that a broad range of cellular functions, including GTPase activity, mitochondrial function and steroid-hormone metabolism, are affected by ATZ. Furthermore, treated mice display enriched histone H3K4me3 marks in regions of strong recombination (double-strand break sites), within very large genes and reduced marks in the pseudoautosomal region of X chromosome.
  
  
  CONCLUSIONS
  Our data demonstrate that atrazine exposure interferes with normal meiosis, which affects spermatozoa production.
authors.affiliation: Inserm U1085 IRSET, 263 Avenue du Général Leclerc, 35042, Rennes, France. aurore.gely-pernot@univ-rennes1.fr.
authors.forename: Aurore
authors.initials: A
authors.lastname: Gely-Pernot
authors.affiliation: Inserm U1085 IRSET, 263 Avenue du Général Leclerc, 35042, Rennes, France. chunxiang.hao@univ-rennes1.fr.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Hao
authors.affiliation: Inserm U1085 IRSET, 263 Avenue du Général Leclerc, 35042, Rennes, France. emmanuelle.becker@univ-rennes1.fr.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Becker
authors.affiliation: Inserm U1085 IRSET, 263 Avenue du Général Leclerc, 35042, Rennes, France. istupa@pbf.hr.|Present address: University of Zagreb, Faculty of Food Technology and Biotechnology, 10000, Zagreb, Croatia. istupa@pbf.hr.
authors.forename: Igor
authors.initials: I
authors.lastname: Stuparevic
authors.affiliation: Inserm U1085 IRSET, 263 Avenue du Général Leclerc, 35042, Rennes, France. christine.kervarrec@inserm.fr.
authors.forename: Christine
authors.initials: C
authors.lastname: Kervarrec
authors.affiliation: Inserm U1085 IRSET, 263 Avenue du Général Leclerc, 35042, Rennes, France. frederic.chalmel@inserm.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chalmel
authors.affiliation: Inserm U1085 IRSET, 263 Avenue du Général Leclerc, 35042, Rennes, France. michael.primig@inserm.fr.
authors.forename: Michael
authors.initials: M
authors.lastname: Primig
authors.affiliation: Inserm U1085 IRSET, 263 Avenue du Général Leclerc, 35042, Rennes, France. bernard.jegou@inserm.fr.|EHESP, Avenue du Professeur Léon-Bernard, 35043, Rennes, France. bernard.jegou@inserm.fr.
authors.forename: Bernard
authors.initials: B
authors.lastname: Jégou
authors.affiliation: Inserm U1085 IRSET, 263 Avenue du Général Leclerc, 35042, Rennes, France. fatima.smagulova@inserm.fr.
authors.forename: Fatima
authors.initials: F
authors.lastname: Smagulova
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001280:Atrazine / Q000494:pharmacology*; D001665:Binding Sites; D002470:Cell Survival; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology / Q000379:methods; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006540:Herbicides / Q000494:pharmacology*; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000187:drug effects* / Q000235:genetics*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D059372:Nucleotide Motifs; D056510:Position-Specific Scoring Matrices; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013076:Sperm Count; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000097:blood
chemical_list: D012739:Gonadal Steroid Hormones; D006540:Herbicides; D006657:Histones; C431936:Nr5a2 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D013739:Testosterone; D020558:GTP Phosphohydrolases; D001280:Atrazine