title: Exposure to low-dose bisphenol A impairs meiosis in the rat seminiferous tubule culture model: a physiotoxicogenomic approach.
abstract: BACKGROUND
  Bisphenol A (BPA) is one of the most widespread chemicals in the world and is suspected of being responsible for male reproductive impairments. Nevertheless, its molecular mode of action on spermatogenesis is unclear. This work combines physiology and toxicogenomics to identify mechanisms by which BPA affects the timing of meiosis and induces germ-cell abnormalities.
  
  
  METHODS
  We used a rat seminiferous tubule culture model mimicking the in vivo adult rat situation. BPA (1 nM and 10 nM) was added to the culture medium. Transcriptomic and meiotic studies were performed on the same cultures at the same exposure times (days 8, 14, and 21). Transcriptomics was performed using pangenomic rat microarrays. Immunocytochemistry was conducted with an anti-SCP3 antibody.
  
  
  RESULTS
  The gene expression analysis showed that the total number of differentially expressed transcripts was time but not dose dependent. We focused on 120 genes directly involved in the first meiotic prophase, sustaining immunocytochemistry. Sixty-two genes were directly involved in pairing and recombination, some of them with high fold changes. Immunocytochemistry indicated alteration of meiotic progression in the presence of BPA, with increased leptotene and decreased diplotene spermatocyte percentages and partial meiotic arrest at the pachytene checkpoint. Morphological abnormalities were observed at all stages of the meiotic prophase. The prevalent abnormalities were total asynapsis and apoptosis. Transcriptomic analysis sustained immunocytological observations.
  
  
  CONCLUSIONS
  We showed that low doses of BPA alter numerous genes expression, especially those involved in the reproductive system, and severely impair crucial events of the meiotic prophase leading to partial arrest of meiosis in rat seminiferous tubule cultures.
authors.affiliation: Institut Méditerranéen de Biodiversité et d'Ecologie marine et continentale (IMBE), Centre National de la Recherche Scientifique (CNRS) UMR 7263/ Institut de Recherche pour le Développement (IRD) 237, Faculté de Médecine, Aix-Marseille Université (AMU), Marseille, France.
authors.forename: Sazan
authors.initials: S
authors.lastname: Ali
authors.affiliation: Institute of Environmental Biology and Biotechnology (IBEB), Life Science division, French Alternative Energy and Atomic Energy Commission (CEA), Marcoule, Bagnols-sur-Cèze, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Steinmetz
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon (IGFL), Centre National de la Recherche Scientifique (CNRS) UMR 5242/ Institut National de la Recherche Agronomique (INRA), Ecole Normale Supérieure de Lyon (ENS), Lyon, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Montillet
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon (IGFL), Centre National de la Recherche Scientifique (CNRS) UMR 5242/ Institut National de la Recherche Agronomique (INRA), Ecole Normale Supérieure de Lyon (ENS), Lyon, France.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Perrard
authors.affiliation: Unité d'Aide Méthodologique à la Recherche clinique, Faculté de Médecine, Aix-Marseille Université (AMU), Marseille, France.
authors.forename: Anderson
authors.initials: A
authors.lastname: Loundou
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon (IGFL), Centre National de la Recherche Scientifique (CNRS) UMR 5242/ Institut National de la Recherche Agronomique (INRA), Ecole Normale Supérieure de Lyon (ENS), Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Durand
authors.affiliation: Institut Méditerranéen de Biodiversité et d'Ecologie marine et continentale (IMBE), Centre National de la Recherche Scientifique (CNRS) UMR 7263/ Institut de Recherche pour le Développement (IRD) 237, Faculté de Médecine, Aix-Marseille Université (AMU), Marseille, France.
authors.forename: Marie-Roberte
authors.initials: MR
authors.lastname: Guichaoua
authors.affiliation: Institute of Environmental Biology and Biotechnology (IBEB), Life Science division, French Alternative Energy and Atomic Energy Commission (CEA), Marcoule, Bagnols-sur-Cèze, France.
authors.forename: Odette
authors.initials: O
authors.lastname: Prat
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D020869:Gene Expression Profiling; D008297:Male; D008540:Meiosis / Q000187:drug effects*; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D010636:Phenols / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D011995:Recombination, Genetic / Q000235:genetics; D015203:Reproducibility of Results; D012671:Seminiferous Tubules / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013090:Spermatocytes / Q000166:cytology / Q000187:drug effects; D013573:Synaptonemal Complex / Q000187:drug effects / Q000235:genetics; D043922:Toxicogenetics; D059467:Transcriptome / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds