Development of a Zebrafish Embryo-Based Test System for Thyroid Hormone System Disruption: 3Rs in Ecotoxicological Research.

IF 3.6 4区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES Environmental Toxicology and Chemistry Pub Date : 2024-05-28 DOI:10.1002/etc.5878

Lisa Gölz, Melanie Blanc-Legendre, Maximilian Rinderknecht, Laura Behnstedt, Sara Coordes, Luisa Reger, Sacha Sire, Xavier Cousin, Thomas Braunbeck, Lisa Baumann

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Abstract

There is increasing concern regarding pollutants disrupting the vertebrate thyroid hormone (TH) system, which is crucial for development. Thus, identification of TH system-disrupting chemicals (THSDCs) is an important requirement in the Organisation for Economic Co-operation and Development (OECD) testing framework. The current OECD approach uses different model organisms for different endocrine modalities, leading to a high number of animal tests. Alternative models compatible with the 3Rs (replacement, reduction, refinement) principle are required. Zebrafish embryos, not protected by current European Union animal welfare legislation, represent a promising model. Studies show that zebrafish swim bladder inflation and eye development are affected by THSDCs, and the respective adverse outcome pathways (AOPs) have been established. The present study compared effects of four THSDCs with distinct molecular modes of action: Propylthiouracil (PTU), potassium perchlorate, iopanoic acid, and the TH triiodothyronine (T3) were tested with a protocol based on the OECD fish embryo toxicity test (FET). Effects were analyzed according to the AOP concept from molecular over morphological to behavioral levels: Analysis of thyroid- and eye-related gene expression revealed significant effects after PTU and T3 exposure. All substances caused changes in thyroid follicle morphology of a transgenic zebrafish line expressing fluorescence in thyrocytes. Impaired eye development and swimming activity were observed in all treatments, supporting the hypothesis that THSDCs cause adverse population-relevant changes. Findings thus confirm that the FET can be amended by TH system-related endpoints into an integrated protocol comprising molecular, morphological, and behavioral endpoints for environmental risk assessment of potential endocrine disruptors, which is compatible with the 3Rs principle. Environ Toxicol Chem 2024;00:1-18. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

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开发基于斑马鱼胚胎的甲状腺激素系统干扰测试系统：生态毒理学研究中的 3R。

人们越来越关注污染物对脊椎动物甲状腺激素（TH）系统的干扰，而甲状腺激素对发育至关重要。因此，在经济合作与发展组织（OECD）的测试框架中，识别干扰甲状腺系统的化学品（THSDCs）是一项重要要求。目前的 OECD 方法针对不同的内分泌模式使用不同的模式生物，导致大量的动物试验。我们需要符合 3R（替代、减少、改进）原则的替代模型。斑马鱼胚胎不受现行欧盟动物福利法规的保护，是一种很有前途的模型。研究表明，斑马鱼的膀胱膨胀和眼睛发育会受到三羟甲基二苯丙胺的影响，并且已经建立了相应的不良后果途径（AOPs）。本研究比较了四种具有不同分子作用模式的 THSDCs 的影响：丙基硫脲嘧啶（PTU）、高氯酸钾、碘帕酸和三碘甲状腺原氨酸（T3）是根据经合组织鱼类胚胎毒性试验（FET）的方案进行测试的。根据 AOP 概念，从分子、形态学和行为学层面对影响进行了分析：对甲状腺和眼睛相关基因表达的分析表明，暴露于 PTU 和 T3 后会产生显著影响。所有物质都会导致在甲状腺细胞中表达荧光的转基因斑马鱼系的甲状腺滤泡形态发生变化。在所有处理中都观察到了眼睛发育和游泳活动受损的现象，这支持了三羟甲基甲状腺激素导致群体相关不良变化的假设。因此，研究结果证实，在对潜在的内分泌干扰物进行环境风险评估时，可以通过TH系统相关终点对FET进行修正，使其成为一个包括分子、形态和行为终点的综合方案，这符合3R原则。环境毒物化学 2024;00:1-18。© 2024 作者。环境毒理学与化学》由 Wiley Periodicals LLC 代表 SETAC 出版。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Environmental Toxicology and Chemistry 环境科学-毒理学

CiteScore

7.40

自引率

9.80%

发文量

265

审稿时长

3.4 months

期刊介绍： The Society of Environmental Toxicology and Chemistry (SETAC) publishes two journals: Environmental Toxicology and Chemistry (ET&C) and Integrated Environmental Assessment and Management (IEAM). Environmental Toxicology and Chemistry is dedicated to furthering scientific knowledge and disseminating information on environmental toxicology and chemistry, including the application of these sciences to risk assessment.[...] Environmental Toxicology and Chemistry is interdisciplinary in scope and integrates the fields of environmental toxicology; environmental, analytical, and molecular chemistry; ecology; physiology; biochemistry; microbiology; genetics; genomics; environmental engineering; chemical, environmental, and biological modeling; epidemiology; and earth sciences. ET&C seeks to publish papers describing original experimental or theoretical work that significantly advances understanding in the area of environmental toxicology, environmental chemistry and hazard/risk assessment. Emphasis is given to papers that enhance capabilities for the prediction, measurement, and assessment of the fate and effects of chemicals in the environment, rather than simply providing additional data. The scientific impact of papers is judged in terms of the breadth and depth of the findings and the expected influence on existing or future scientific practice. Methodological papers must make clear not only how the work differs from existing practice, but the significance of these differences to the field. Site-based research or monitoring must have regional or global implications beyond the particular site, such as evaluating processes, mechanisms, or theory under a natural environmental setting.

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