Histochemistry and Cell Biology

, Volume 137, Issue 2, pp 249–259 | Cite as

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

  • Hu-He Chao
  • Xi-Feng Zhang
  • Bo Chen
  • Bo Pan
  • Lian-Jun Zhang
  • Lan Li
  • Xiao-Feng Sun
  • Qing-Hua Shi
  • Wei ShenEmail author
Original Paper


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.


Bisphenol 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.

Supplementary material

418_2011_894_MOESM1_ESM.ppt (278 kb)
Supplemental Figure 1. Genomic region analyzed for Igf2r, Peg3 and H19 genes (PPT 274 kb)
418_2011_894_MOESM2_ESM.ppt (612 kb)
Supplemental Figure 2. The immunohistochemistry analysis of the ovaries from BPA-treated mice (oocyte cytoplasm was labeled by a STAT3 antibody, and nuclei were stained by hematoxylin). Scale bar, 100 μm (PPT 612 kb)
418_2011_894_MOESM3_ESM.ppt (202 kb)
Supplemental Figure 3. BPA did not affect the DNA methylation of estrogen receptor gene promoter region. Circles: CpG sites within the regions analyzed; filled circles: methylated cytosines; open circles: unmethylated cytosines (PPT 200 kb)
418_2011_894_MOESM4_ESM.doc (36 kb)
Supplemental Table 1 (DOC 36 kb)
418_2011_894_MOESM5_ESM.doc (40 kb)
Supplemental Table 2 (DOC 39 kb)
418_2011_894_MOESM6_ESM.doc (56 kb)
Supplemental Table 3 (DOC 56 kb)
418_2011_894_MOESM7_ESM.doc (59 kb)
Supplemental Table 4 (DOC 59 kb)


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Hu-He Chao
    • 1
  • Xi-Feng Zhang
    • 2
  • Bo Chen
    • 1
  • Bo Pan
    • 1
  • Lian-Jun Zhang
    • 1
  • Lan Li
    • 1
  • Xiao-Feng Sun
    • 1
  • Qing-Hua Shi
    • 3
  • Wei Shen
    • 1
    Email author
  1. 1.Laboratory of Germ Cell Biology, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of ShandongQingdao Agricultural UniversityQingdaoChina
  2. 2.College of Biological and Pharmaceutical EngineeringWuhan Polytechnic UniversityWuhanChina
  3. 3.Hefei National Laboratory for Physical Sciences at Microscale and School of Life SciencesUniversity of Science and Technology of ChinaHefeiChina

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