Epigenetic impacts of endocrine disruptors in the brain.
Epigenetic impacts of endocrine disruptors in the brain.
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DOI：
10.1016/j.yfrne.2016.09.002
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发表时间：
2017-01
影响因子：
7.4
通讯作者：
Gore AC
中科院分区：
文献类型：
--
作者：
Walker DM;Gore AC
生殖能力的获得是由类固醇激素在发育的关键窗口期间作用于下丘脑而组织和激活的。本文综述了表观遗传过程的潜在作用，特别是DNA甲基化，在调节性分化的下丘脑激素。我们研究了内分泌干扰化学物质（EDCs）以年龄，性别和区域特异性方式破坏这些过程，重点关注围产期EDCs如何通过表观遗传机制重新编程DNA甲基化和性类固醇激素受体表达。这些受体是大脑性别分化所必需的，它们的表达改变可能是生殖生理和行为中断的基础。最后，我们回顾了有关组蛋白修饰和非编码RNA参与脑性别分化及其受内分泌干扰的文献。通过将这些数据纳入性别和发育背景，我们得出结论，围产期EDC暴露以性别特异性方式改变生殖神经内分泌系统的发育轨迹。
The acquisition of reproductive competence is organized and activated by steroid hormones acting upon the hypothalamus during critical windows of development. This review describes the potential role of epigenetic processes, particularly DNA methylation, in the regulation of sexual differentiation of the hypothalamus by hormones. We examine disruption of these processes by endocrine-disrupting chemicals (EDCs) in an age-, sex-, and region-specific manner, focusing on how perinatal EDCs act through epigenetic mechanisms to reprogram DNA methylation and sex steroid hormone receptor expression throughout life. These receptors are necessary for brain sexual differentiation and their altered expression may underlie disrupted reproductive physiology and behavior. Finally, we review the literature on histone modifications and non-coding RNA involvement in brain sexual differentiation and their perturbation by EDCs. By putting these data into a sex and developmental context we conclude that perinatal EDC exposure alters the developmental trajectory of reproductive neuroendocrine systems in a sex-specific manner.