Are endocrine disrupting compounds environmental risk factors for autism spectrum disorder?
Are endocrine disrupting compounds environmental risk factors for autism spectrum disorder?
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DOI：
10.1016/j.yhbeh.2017.10.003
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发表时间：
2018-05
影响因子：
3.5
通讯作者：
Hu VW
中科院分区：
文献类型：
--
作者：
Moosa A;Shu H;Sarachana T;Hu VW
最近对自闭症谱系障碍（ASD）病因学的研究已经部分地从单一关注遗传原因转向环境因素及其基因相互作用的参与。这种焦点的转变是ASD患病率迅速增加以及这种疾病在同卵双胞胎中不完全外显的结果。其中一个以环境为重点的研究领域是暴露于内分泌干扰化合物（EDCs）与ASD风险升高的关联。内分泌干扰物是一种外源性化学物质，可以改变内源性激素的活性和体内平衡，从而在人类发育的各个阶段潜在地破坏性激素和其他天然激素的作用。由于性激素在大脑发育和性别分化中起着重要作用，在发育的关键阶段，子宫内暴露于内分泌干扰物可能对发育中的胎儿产生持久的神经和其他生理影响，最终影响儿童和成人。本综述将重点关注内分泌干扰物对自闭症风险和发病机制的可能贡献，首先讨论内源性性激素对自闭症表型的影响，然后回顾人类暴露于内分泌干扰物的记录以及与ASD相关行为的关系。EDC暴露和异常的神经发育和行为之间的机制联系，然后考虑，重点是EDC诱导的转录档案来自动物和细胞研究。最后，本综述将讨论EDC暴露可能导致基因表达和表型持续变化的可能机制，这可能反过来有助于ASD的跨代遗传。
Recent research on the etiology of autism spectrum disorder (ASD) has shifted in part from a singular focus on genetic causes to the involvement of environmental factors and their gene interactions. This shift in focus is a result of the rapidly increasing prevalence of ASD coupled with the incomplete penetrance of this disorder in monozygotic twins. One such area of environmentally focused research is the association of exposures to endocrine disrupting compounds (EDCs) with elevated risk for ASD. EDCs are exogenous chemicals that can alter endogenous hormone activity and homeostasis, thus potentially disrupting the action of sex and other natural hormones at all stages of human development. Inasmuch as sex hormones play a fundamental role in brain development and sexual differentiation, exposure to EDCs in utero during critical stages of development can have lasting neurological and other physiological influences on the developing fetus and, ultimately, the child as well as adult. This review will focus on the possible contributions of EDCs to autism risk and pathogenesis by first discussing the influence of endogenous sex hormones on the autistic phenotype, followed by a review of documented human exposures to EDCs and associations with behaviors relevant to ASD. Mechanistic links between EDC exposures and aberrant neurodevelopment and behaviors are then considered, with emphasis on EDC-induced transcriptional profiles derived from animal and cellular studies. Finally, this review will discuss possible mechanisms through which EDC exposure can lead to persistent changes in gene expression and phenotype, which may in turn contribute to transgenerational inheritance of ASD.
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DOI：
10.1038/nrendo.2016.186
发表时间：
2017-03
期刊：
Nature reviews. Endocrinology
影响因子：
--
作者：
Braun JM
通讯作者：
Braun JM
影响因子：
10.4
作者：
Braun JM;Kalkbrenner AE;Just AC;Yolton K;Calafat AM;Sjödin A;Hauser R;Webster GM;Chen A;Lanphear BP
通讯作者：
Lanphear BP
影响因子：
6.9
作者：
BAILEY, A;LECOUTEUR, A;RUTTER, M
通讯作者：
RUTTER, M
影响因子：
10.4
作者：
Chevrier, Jonathan;Gunier, Robert B.;Harley, Kim G.
通讯作者：
Harley, Kim G.
影响因子：
4.5
作者：
Berko, Esther R.;Suzuki, Masako;Greally, John M.
通讯作者：
Greally, John M.