Bisphenol A exposure modifies methylation of imprinted genes in mouse oocytes via the estrogen receptor signaling pathway

Histochem Cell Biol. 2012 Feb;137(2):249-59. doi: 10.1007/s00418-011-0894-z. Epub 2011 Dec 1.


Bisphenol A (BPA), a synthetic additive used to harden polycarbonate plastics and epoxy resin, is ubiquitous in our everyday environment. Many studies have indicated detrimental effects of BPA on the mammalian reproductive abilities. This study is aimed to test the potential effects of BPA on methylation of imprinted genes during oocyte growth and meiotic maturation in CD-1 mice. Our results demonstrated that BPA exposure resulted in hypomethylation of imprinted gene Igf2r and Peg3 during oocyte growth, and enhanced estrogen receptor (ER) expression at the levels of mRNA and protein. The relationship between ER expression and imprinted gene hypomethylation was substantiated using an ER inhibitor, ICI182780. In addition, BPA promoted the primordial to primary follicle transition, thereby speeding up the depletion of the primordial follicle pool, and suppressed the meiotic maturation of oocytes because of abnormal spindle assembling in meiosis I. In conclusion, neonatal exposure to BPA inhibits methylation of imprinted genes during oogenesis via the ER signaling pathway in CD-1 mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds
  • DNA Methylation / drug effects*
  • DNA Methylation / genetics
  • Female
  • Genomic Imprinting / drug effects
  • Genomic Imprinting / genetics*
  • Kruppel-Like Transcription Factors / drug effects
  • Kruppel-Like Transcription Factors / genetics*
  • Mice
  • Oocytes / drug effects
  • Oocytes / growth & development
  • Oocytes / metabolism*
  • Oogenesis / drug effects
  • Oogenesis / genetics
  • Ovarian Follicle / drug effects
  • Ovarian Follicle / physiology
  • Phenols / toxicity*
  • Receptor, IGF Type 2 / drug effects
  • Receptor, IGF Type 2 / genetics*
  • Receptors, Estrogen / drug effects
  • Receptors, Estrogen / metabolism*
  • Signal Transduction


  • Benzhydryl Compounds
  • Kruppel-Like Transcription Factors
  • Peg3 protein, mouse
  • Phenols
  • Receptor, IGF Type 2
  • Receptors, Estrogen
  • bisphenol A