[化学物质引起的围产期甲状腺激素紊乱和大脑发育逆境:旨在开发新的评估方法的努力现状]。

Tomoya Yamada
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引用次数: 0

摘要

胎儿甲状腺激素(THs)对大脑发育至关重要,主要依赖于母体的供应。临床研究表明,孕妇体内的促甲状腺激素改变会对其孩子的神经发育产生永久性影响,这表明导致母体促甲状腺激素紊乱的化学物质可能需要调节。然而,化学物质诱导的母体TH减少与胎儿脑TH破坏以及胎儿脑发育异常之间的定量关系尚不完全清楚。因此,需要一种能够精确、快速和定量地评估可能导致大脑异常的测试化学品的th干扰效应的方法。目前,已知TH破坏不良结果通路(AOPs)中的多个分子启动事件(MIEs),并且正在开发使用新方法方法的测试来研究化学物质对这些MIEs的影响。此外,比较甲状腺测定(CTA)有望用于比较评估血TH浓度的降低,通常是由于多种MIEs的作用导致的,在母鼠及其后代中。最近,由于越来越需要更精确和有效的评估和减少动物试验,我们一直致力于改进CTA。我们提出了一种改进的CTA,增加了新的测试项目:脑TH浓度和异位(脑TH缺乏的组织学标志),同时减少了50%的动物数量。可行性研究证实,它可以检测到后代大脑中约20-30%的TH破坏。这篇综述概述了目前努力开发新的评估方法围产期TH干扰的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Chemical-induced perinatal thyroid hormone disruption and brain developmental adversity: status of efforts aimed at developing new evaluation methods].

Fetal thyroid hormones (THs), essential for brain development, largely depend on maternal supply. Clinical studies have shown that TH alterations in pregnant mothers can lead to permanent neurodevelopmental effects in their children, suggesting that chemicals causing maternal TH disruption may require regulation. However, the quantitative relationship between chemical-induced maternal TH reductions and fetal brain TH disruption, as well as fetal brain developmental abnormalities, is not fully understood. Thus, there is a need for methods that can precisely, rapidly, and quantitatively evaluate TH-disrupting effects of test chemicals that may cause brain abnormalities. Currently, multiple molecular initiating events (MIEs) in the adverse outcome pathways (AOPs) of TH disruption are known, and tests using New Approach Methodologies are being developed to investigate the effects of chemicals on these MIEs. Additionally, the Comparative Thyroid Assay (CTA) is expected to be utilized to comparatively evaluate the decrease in blood TH concentrations, commonly observed as a result of actions on multiple MIEs, in maternal rats along with their offspring. Recently, due to the increasing need for more precise and efficient evaluations and the reduction of animal testing, we have worked on improving the CTA. We proposed a modified CTA that adds new test items: brain TH concentrations and heterotopia (a histological marker of brain TH deficiency), while reducing the number of animals used by 50%. Feasibility studies confirmed that it can detect approximately 20-30% TH disruption in the offspring brain. This review outlines the current efforts to develop new evaluation methods for perinatal TH disruption effects.

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来源期刊
Folia Pharmacologica Japonica
Folia Pharmacologica Japonica Pharmacology, Toxicology and Pharmaceutics-Pharmacology
CiteScore
0.40
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0.00%
发文量
132
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