Bisphenol A exposure modifies methylation of imprinted genes in mouse oocytes via the estrogen receptor signaling pathway
- 1.2k Downloads
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.
KeywordsBisphenol A Oocytes Imprint genes DNA methylation Estrogen receptor
This work was supported by grants from the National Basic Research Program of China (973 Program, 2012CB944401, 2011CB944501 and 2007CB947401), National Nature Science Foundation (31001010, 31171376 and 31101716), Foundation of Shandong Provincial Education Department (J11LC20), Foundation of Distinguished Young Scholars (JQ201109) and Foundation of Taishan Scholar of Shandong Province.
Conflict of interest
These authors fully declare any financial or other potential conflict of interest.
- Lutz LB, Cole LM, Gupta MK, Kwist KW, Auchus RJ, Hammes SR (2001) Evidence that androgens are the primary steroids produced by Xenopus laevis ovaries and may signal through the classical androgen receptor to promote oocyte maturation. Proc Natl Acad Sci USA 98:13728–13733PubMedCrossRefGoogle Scholar