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Long-Term Effects of Early-Life Exposure to Environmental Oestrogens on Ovarian Function: Role of Epigenetics

机译:生命早期暴露于环境雌激素对卵巢功能的长期影响:表观遗传学的作用

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Oestrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is considered that developmental exposure to environmental oestrogens can disrupt neural and reproductive tract development, potentially resulting in long-term alterations in neurobehaviour and reproductive function. Many chemicals have been shown to have oestrogenic activity, whereas others affect oestrogen production and turnover, resulting in the disruption of oestrogen signalling pathways. However, these mechanisms and the concentrations required to induce these effects cannot account for the myriad adverse effects of environmental toxicants on oestrogen-sensitive target tissues. Hence, alternative mechanisms are assumed to underlie the adverse effects documented in experimental animal models and thus could be important to human health. In this review, the epigenetic regulation of gene expression is explored as a potential target of environmental toxicants including oestrogenic chemicals. We suggest that toxicant-induced changes in epigenetic signatures are important mechanisms underlying the disruption of ovarian follicular development. In addition, we discuss how exposure to environmental oestrogens during early life can alter gene expression through effects on epigenetic control potentially leading to permanent changes in ovarian physiology.
机译:雌激素在大脑和生殖道的发育和功能中起重要作用。因此,据认为发育暴露于环境雌激素可破坏神经和生殖道发育,潜在地导致神经行为和生殖功能的长期改变。已显示许多化学物质具有雌激素活性,而其他化学物质会影响雌激素的产生和更新,从而导致雌激素信号传导途径的破坏。但是,这些机制和诱导这些作用所需的浓度不能解释环境毒物对雌激素敏感性靶组织的无数不利作用。因此,假定替代机制是实验动物模型中记录的不良作用的基础,因此可能对人类健康很重要。在这篇综述中,探索了基因表达的表观遗传调控作为环境毒性物质(包括雌激素化学物质)的潜在目标。我们建议,有毒物质引起的表观遗传学特征的变化是破坏卵巢卵泡发育的重要机制。此外,我们讨论了在生命早期暴露于环境雌激素下如何通过对表观遗传控制的影响来改变基因表达,从而可能导致卵巢生理的永久性变化。

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