Bisphenol A accelerates meiotic progression in embryonic chickens via the estrogen receptor β signaling pathway

Gen Comp Endocrinol. 2018 Apr 1:259:66-75. doi: 10.1016/j.ygcen.2017.11.004. Epub 2017 Nov 4.

Abstract

Bisphenol A (BPA) as an endocrine-disrupting chemical with weak estrogenic activity affects formation of primordial follicles. This study aimed to identify the potential effects and molecular mechanisms of BPA on meiosis and primordial follicle formation in chickens. The results suggest that the cortical layer was thickened and the number of germ cells that entered into meiosis was increased in BPA-treated ovaries. The percentage of γH2AX-positive cells increased significantly. In addition, up-regulated mRNA expression of meiotic genes, including stimulated by retinoic acid gene 8 (Stra8), disrupted meiotic cDNA 1 homologue (Dmc1) and synaptonemal complex protein 3 (Scp3) were observed in BPA-treated ovaries. Therefore, progression to meiosis prophase I was accelerated by exposure to BPA. Furthermore, the results demonstrated that injection of BPA resulted in hypomethylation of Dazl (Deleted in A Zoospermia-Like gene) and Stra8 and up-regulation mRNA expression of Dazl and Stra8 during meiotic onset. Finally, the relationship between estrogen receptor (ER) expression and BPA-induced meiosis was revealed using an in vitro ovarian culture system. BPA enhanced ERβ expression at the levels of mRNA and protein, while BPA exerted no significant effect on ERα and membrane-bound estrogen receptor (GPR30) expression. The inducing effects of BPA on meiosis were blocked by ER inhibitor. Collectively, these results demonstrate the dynamic ovarian response to BPA exposure, which indicate that BPA affects the formation of primordial follicles by promoting meiotic progression of oocytes via hypomethylation of Dazl and Stra8 and ERβ signaling pathways.

Keywords: Bisphenol A; Chickens; DNA methylation; Estrogen receptor β; Meiosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / toxicity*
  • Chick Embryo
  • Chickens / metabolism*
  • DNA / metabolism
  • DNA Methylation / genetics
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / genetics
  • Estrogen Receptor beta / metabolism*
  • Female
  • Gene Expression Regulation / drug effects
  • Germ Cells / cytology
  • Germ Cells / drug effects
  • Germ Cells / metabolism
  • Meiosis / drug effects*
  • Ovarian Follicle / cytology
  • Ovarian Follicle / drug effects
  • Ovarian Follicle / metabolism
  • Phenols / toxicity*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects*

Substances

  • Benzhydryl Compounds
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Phenols
  • RNA, Messenger
  • DNA
  • bisphenol A