title: Exposure of preimplantation embryos to low-dose bisphenol A impairs testes development and suppresses histone acetylation of StAR promoter to reduce production of testosterone in mice.
abstract: Previous studies have shown that bisphenol A (BPA) is a potential endocrine disruptor and testicular toxicant. The present study focused on exploring the impact of exposure to low dose of BPA on male reproductive development during the early embryo stage and the underlying mechanisms. BPA (20 μg/kg/day) was orally administered to female mice on days 1-5 of gestation. The male offspring were euthanized at PND10, 20, 24, 35 or PND50. We found that the mice exposed to BPA before implantation (BPA-mice) displayed retardation of testicular development with reduction of testosterone level. The diameter and epithelium height of seminiferous tubules were reduced in BPA-mice at PND35. The numbers of spermatogenic cells at different stages were significantly reduced in BPA-mice at PND50. BPA-mice showed a persistent reduction in serum and testicular testosterone levels starting from PND24, whereas GnRH mRNA was significantly increased at PND35 and PND50. The expressions of testicular StAR and P450scc in BPA-mice also decreased relative to those of the controls at PND35 and PND50. Further analysis found that the levels of histone H3 and H3K14 acetylation (Ac-H3 and H3K14ac) in the promoter of StAR were decreased relative to those of control mice, whereas the level of Ac-H3 in the promoter of P450scc was not significantly different between the groups. These results provide evidence that exposure to BPA in preimplantation embryo retards the development of testes by reducing histone acetylation of the StAR promoter to disrupt the testicular testosterone synthesis.
authors.affiliation: State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, 210029, China; Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.affiliation: Centre for Reproductive Medicine, Wuxi Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, 214002, China.
authors.forename: Yinyang
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 210029, China. Electronic address: lyglyc100@njmu.edu.cn.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, 210029, China; Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 210029, China. Electronic address: lingchen@njmu.edu.cn.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
mesh_terms: D000107:Acetylation; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001755:Blastocyst / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010636:Phenols / Q000494:pharmacology*; D010750:Phosphoproteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D012708:Sertoli Cells / Q000187:drug effects; D012733:Sex Differentiation / Q000187:drug effects / Q000235:genetics; D013737:Testis / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis*; D000098682:Steroidogenic Acute Regulatory Protein; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D012739:Gonadal Steroid Hormones; D006657:Histones; D010636:Phenols; D010750:Phosphoproteins; D013739:Testosterone; D000098682:Steroidogenic Acute Regulatory Protein; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Histone acetylation; Preimplantation embryo; StAR; Testes; Testosterone