Sex-Specific Effects of Combined Exposure to Chemical and Non-chemical Stressors on Neuroendocrine Development: a Review of Recent Findings and Putative Mechanisms.
Sex-Specific Effects of Combined Exposure to Chemical and Non-chemical Stressors on Neuroendocrine Development: a Review of Recent Findings and Putative Mechanisms.
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DOI：
10.1007/s40572-017-0165-9
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发表时间：
2017-12
影响因子：
7.9
通讯作者：
Wright RJ
中科院分区：
文献类型：
--
作者：
Cowell WJ;Wright RJ
环境毒物和社会心理压力源有许多共同的生物基础，并影响重叠的生理途径。越来越多的证据表明，压力引起的母体环境变化可能会使快速发育的生理系统因同时或随后暴露于环境化学物质而受到破坏。在这篇综述中，我们强调了发育中的神经内分泌系统对压力或压力相关物质和环境毒物（双酚A、酒精、邻苯二甲酸盐、铅、毒死蜱和交通相关空气污染）联合效应的性别特异性易感性的推测机制。我们提供的证据表明，在快速发育窗口期间，同时或串联暴露于化学和非化学应激源与性别特异性的协同、增强和逆转效应有关，这些效应与下丘脑-垂体-肾上腺轴功能、性类固醇水平、神经递质回路和先天免疫功能有关。我们还发现了空白，例如内分泌活性胎盘在我们对这些复杂相互作用的理解中所起的作用。最后，我们讨论了未来的研究需求，包括对非激素应激生物标志物的研究。我们证明了男性和女性的多种生理系统受到化学和非化学压力源的联合暴露的不同影响。总的来说，这些结果强调了在研究神经内分泌系统时评估性别特异性终点的重要性，并强调了在社会环境背景下检查化学毒物暴露的必要性。
Environmental toxicants and psychosocial stressors share many biological substrates and influence overlapping physiological pathways. Increasing evidence indicates stress-induced changes to the maternal milieu may prime rapidly developing physiological systems for disruption by concurrent or subsequent exposure to environmental chemicals. In this review, we highlight putative mechanisms underlying sex-specific susceptibility of the developing neuroendocrine system to the joint effects of stress or stress correlates and environmental toxicants (bisphenol A, alcohol, phthalates, lead, chlorpyrifos and traffic-related air pollution). We provide evidence indicating that concurrent or tandem exposure to chemical and non-chemical stressors during windows of rapid development is associated with sex-specific synergistic, potentiated and reversed effects on several neuroendocrine endpoints related to hypothalamic-pituitary-adrenal axis function, sex steroid levels, neurotransmitter circuits and innate immune function. We additionally identify gaps, such as the role that the endocrine-active placenta plays, in our understanding of these complex interactions. Finally, we discuss future research needs, including the investigation of non-hormonal biomarkers of stress. We demonstrate multiple physiologic systems are impacted by joint exposure to chemical and non-chemical stressors differentially among males and females. Collectively, the results highlight the importance of evaluating sex-specific endpoints when investigating the neuroendocrine system and underscore the need to examine exposure to chemical toxicants within the context of the social environment.