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Bisphenol A Effects on Mammalian Oogenesis and Epigenetic Integrity of Oocytes: A Case Study Exploring Risks of Endocrine Disrupting Chemicals

机译:双酚对哺乳动物的卵母细胞哺乳动物的影响以及卵母细胞的表观完整性:一种探讨内分泌扰乱化学品的风险

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摘要

Bisphenol A (BPA), originally developed as a synthetic oestrogen, is nowadays extensively used in the production of polymeric plastics. Under harsh conditions, these plastics may release BPA, which then can leach into the environment. Detectable concentrations of BPA have been measured in most analysed samples of human serum, plasma, or urine, as well as in follicular fluid, foetal serum, and amniotic fluid. Here we summarize the evidence about adverse BPA effects on the genetic and epigenetic integrity of mammalian oocytes. We conclude that increasing evidence supports the notion that low BPA concentrations adversely affect the epigenome of mammalian female germ cells, with functional consequences on gene expression, chromosome dynamics in meiosis, and oocyte development. Specific time windows, during which profound chromatin remodelling occurs and maternal imprints are established or protected, appear particularly vulnerable to epigenetic deregulation by BPA. Transgenerational effects have been also observed in the offspring of BPA-treated rodents, although the epigenetic mechanisms of inheritance still need to be clarified. The relevance of these findings for human health protection still needs to be fully assessed, but they warrant further investigation in both experimental models and humans.
机译:如今,最初开发为合成雌激素的双酚A(BPA)在聚合物塑料的生产中是广泛的。在恶劣的条件下,这些塑料可能释放BPA,然后可以将其浸入环境中。在大多数分析的人血清,血浆或尿液中的样品以及滤泡液,胎儿血清和羊水中测量了可检测的BPA浓度。在这里,我们总结了对哺乳动物卵母细胞遗传和表观遗传完整性的对不良BPA影响的证据。我们得出结论,越来越多的证据支持低BPA浓度对哺乳动物雌性生殖细胞的外观蛋白酶产生的概念影响,具有对基因表达,染色体动力学和卵母细胞发育的功能后果。特定时间窗口,在此期间发生深度染色质重塑和母体印记,或保护母体印记,特别容易受到BPA的表观遗传失调。在BPA处理的啮齿动物的后代也观察到转基因效应,尽管遗传的表观遗传机制仍然需要澄清。这些调查结果对人类健康保护的相关性仍需要完全评估,但他们在实验模型和人类中进行进一步调查。

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