Disruption in Thyroid Signaling Pathway: A Mechanism for the Effect of Endocrine-Disrupting Chemicals on Child Neurodevelopment.
Disruption in Thyroid Signaling Pathway: A Mechanism for the Effect of Endocrine-Disrupting Chemicals on Child Neurodevelopment.
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DOI：
10.3389/fendo.2018.00204
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发表时间：
2018
影响因子：
5.2
通讯作者：
Trasande L
中科院分区：
文献类型：
--
作者：
Ghassabian A;Trasande L
甲状腺激素对正常的大脑发育至关重要。怀孕期间短暂和轻度甲状腺激素不足也与后代神经发育受损有关（例如，3-4的智商分数下降与母亲游离甲状腺素最低的第五百分位有关）。虽然碘摄入不足仍然是包括孕妇在内的弱势群体轻度甲状腺激素不足的最常见潜在原因，但暴露于环境污染物等其他因素最近引起了越来越多的关注，特别是与碘缺乏的相互作用。干扰内分泌的化学物质（EDCs）是天然和合成的物质，在儿童和成人包括孕妇中普遍存在。EDCs通过结合激素受体和改变基因表达，暂时或永久地干扰内分泌系统中的激素信号通路。其他机制包括激素的产生、代谢和转移的改变。实验研究表明，暴露于EDCs会影响各种脑过程，如神经发生、神经分化和迁移以及神经连通性。神经影像学研究证实，在标准使用水平的EDC暴露下，脑形态学异常（如皮质变薄）与神经发育障碍相一致。在这篇综述中，我们概述了目前关于EDCs抗甲状腺作用的毒理学和人体研究的发现，并特别关注胎儿和儿童早期暴露。这篇简短的综述强调了需要进行更多的多学科研究，重点关注甲状腺功能紊乱作为EDC发育性神经毒性的潜在机制，这可以为儿童发育迟缓的可改变危险因素提供见解。
Thyroid hormones are crucial in normal brain development. Transient and mild thyroid hormone insufficiency in pregnancy is also associated with impaired neurodevelopment in the offspring (e.g., 3–4 IQ score loss in association with maternal free thyroxine in the lowest fifth percentile). While inadequate iodine intake remains the most common underlying cause of mild thyroid hormone insufficiency in vulnerable populations including pregnant women, other factors such as exposure to environmental contaminants have recently attracted increasing attention, in particular in interaction with iodine deficiency. Endocrine-disrupting chemicals (EDCs) are natural and synthetic substances with ubiquitous exposure in children and adults including pregnant women. EDCs interfere, temporarily or permanently, with hormonal signaling pathways in the endocrine system by binding to hormone receptors and modifying gene expression. Other mechanisms involve alterations in production, metabolism, and transfer of hormones. Experimental studies have shown that exposures to EDCs affect various brain processes such as neurogenesis, neural differentiation and migration, as well as neural connectivity. Neuroimaging studies confirm brain morphological abnormalities (e.g., cortical thinning) consistent with neurodevelopmental impairments as a result of EDC exposures at standard use levels. In this review, we provide an overview of present findings from toxicological and human studies on the anti-thyroid effect of EDCs with a specific attention to fetal and early childhood exposure. This brief overview highlights the need for additional multidisciplinary studies with a focus on thyroid disruption as an underlying mechanism for developmental neurotoxicity of EDC, which can provide insight into modifiable risk factors of developmental delays in children.
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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：
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通讯作者：
Braun JM
DOI：
10.1186/1476-069x-13-106
发表时间：
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期刊：
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影响因子：
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影响因子：
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影响因子：
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影响因子：
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作者：
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