Bisphenol A exposure modifies methylation of imprinted genes in mouse oocytes via the estrogen receptor signaling pathway
Bisphenol A exposure modifies methylation of imprinted genes in mouse oocytes via the estrogen receptor signaling pathway
复制标题
双酚 A 暴露通过雌激素受体信号通路改变小鼠卵母细胞中印记基因的甲基化
DOI：
10.1007/s00418-011-0894-z
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发表时间：
2012-02-01
影响因子：
2.3
通讯作者：
Shen, Wei
中科院分区：
文献类型：
--
作者：
Chao, Hu-He;Zhang, Xi-Feng;Shen, Wei
双酚A（BPA）是一种用于硬化聚碳酸酯塑料和环氧树脂的合成添加剂，在我们的日常环境中无处不在。许多研究表明BPA对哺乳动物的生殖能力有不利影响。本研究旨在检测BPA对CD-1小鼠卵母细胞生长和减数分裂成熟过程中印迹基因甲基化的潜在影响。结果表明，BPA暴露导致卵母细胞生长过程中印迹基因Igf 2和Peg 3的低甲基化，增强雌激素受体（ER）在mRNA和蛋白水平的表达。使用ER抑制剂ICI 182780证实了ER表达和印迹基因低甲基化之间的关系。此外，BPA还促进了原始卵泡向初级卵泡的转变，从而加速了原始卵泡池的消耗，并由于减数分裂Ⅰ纺锤体组装异常而抑制了卵母细胞的减数分裂成熟。总之，新生儿暴露于BPA抑制甲基化的印记基因在卵子发生过程中通过ER信号通路在CD-1小鼠。
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 geneIgf2randPeg3during 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.