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内分泌干扰化学品对神经发育的影响:需要更好的内分泌干扰诱导发育神经毒性测试策略。

Impact of endocrine disrupting chemicals on neurodevelopment: the need for better testing strategies for endocrine disruption-induced developmental neurotoxicity.

机构信息

Department of Organismal Biology, Uppsala University, Sweden.

Department of Biochemistry and Biophysics, Stockholm University, Sweden.

出版信息

Expert Rev Endocrinol Metab. 2022 Mar;17(2):131-141. doi: 10.1080/17446651.2022.2044788. Epub 2022 Mar 7.

Abstract

INTRODUCTION

Brain development is highly dependent on hormonal regulation. Exposure to chemicals disrupting endocrine signaling has been associated with neurodevelopmental impairment. This raises concern about exposure to the suspected thousands of endocrine disruptors, and has resulted in efforts to improve regulation of these chemicals. Yet, the causal links between endocrine disruption and developmental neurotoxicity, which would be required for regulatory action, are still largely missing.

AREAS COVERED

In this review, we illustrate the importance of two endocrine systems, thyroid hormone and retinoic acid pathways, for neurodevelopment. We place special emphasis on TH and RA synthesis, metabolism, and how endocrine disrupting chemicals known or suspected to affect these systems are associated with developmental neurotoxicity.

EXPERT OPINION

While it is clear that neurodevelopment is dependent on proper hormonal functioning, and evidence is increasing for developmental neurotoxicity induced by endocrine disrupting chemicals, this is not grasped by current chemical testing. Thus, there is an urgent need to develop test methods detecting endocrine disruption in the context of neurodevelopment. Key to this development is further mechanistic insights on the involvement of endocrine signaling in neurodevelopment as well as increased support to develop and validate new test methods for the regulatory context.

摘要

简介

大脑发育高度依赖于激素调节。接触到干扰内分泌信号的化学物质已被认为与神经发育障碍有关。这引发了人们对接触疑似数千种内分泌干扰物的担忧,并促使人们努力改善对这些化学物质的监管。然而,内分泌干扰与发育神经毒性之间的因果关系(这是监管行动所必需的)在很大程度上仍然缺失。

涵盖领域

在这篇综述中,我们说明了甲状腺激素和视黄酸途径这两个内分泌系统对神经发育的重要性。我们特别强调了 TH 和 RA 的合成、代谢,以及已知或怀疑会影响这些系统的内分泌干扰化学物质如何与发育神经毒性相关。

专家意见

虽然很明显,神经发育依赖于适当的激素功能,并且越来越多的证据表明内分泌干扰化学物质会导致发育神经毒性,但这并没有被当前的化学测试所捕捉到。因此,迫切需要开发在神经发育背景下检测内分泌干扰的测试方法。这一发展的关键是进一步深入了解内分泌信号在神经发育中的作用机制,并增加对开发和验证新的监管测试方法的支持。

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