Division of Pharmacology and Toxicology, University of Texas at Austin, Austin, TX, United States.
Division of Pharmacology and Toxicology, University of Texas at Austin, Austin, TX, United States; Institute for Neuroscience, University of Texas at Austin, Austin, TX, United States.
Adv Pharmacol. 2021;92:73-99. doi: 10.1016/bs.apha.2021.03.006. Epub 2021 May 10.
Endocrine-disrupting chemicals (EDCs) are a major public health concern, yet there are gaps in knowledge about the mechanisms for their effects. The brain is incredibly sensitive to small changes in the hormonal environment during early development, with natural sex differences in gonadal hormones shaping the organization of sex-specific neural circuits early in life. EDC exposure during these periods can lead to lifelong impacts on neurobiological health outcomes. Recently, epigenetic mechanisms have been proposed as a potential molecular mechanism for effects of endogenous hormones on the organization of developing brain circuits, leading to speculation that these mechanisms may underlie the long-term impacts of EDC exposure. Of these mechanisms, DNA methylation, associated with gene suppression, and histone marks, associated with gene suppression or activation, will be discussed. We review the evidence for hormones and their role in brain sexual differentiation; underlying epigenetic mechanisms; and how two classes of estrogenic EDCs, BPA and PCBs, may interfere with these processes to change brain structure and function.
内分泌干扰化学物质（EDCs）是一个主要的公共卫生关注点，但对于它们作用的机制仍存在知识缺口。在早期发育过程中，大脑对激素环境的微小变化非常敏感，而性腺激素的天然性别差异会在生命早期塑造特定性别的神经回路的组织。在此期间暴露于 EDC 会导致对神经生物学健康结果的终生影响。最近，表观遗传机制被提出作为内源性激素对发育中大脑回路组织作用的潜在分子机制，这导致人们推测这些机制可能是 EDC 暴露的长期影响的基础。在这些机制中，将讨论与基因抑制相关的 DNA 甲基化和与基因抑制或激活相关的组蛋白标记。我们回顾了激素及其在大脑性别分化中的作用、潜在的表观遗传机制，以及两种类雌激素 EDC（BPA 和 PCB）如何干扰这些过程以改变大脑结构和功能的证据。
