测试青鳉转基因刺五加胚胎甲状腺特异性测定（TETHYS）对不同作用机制的敏感性

IF 4.1 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology Pub Date : 2024-09-10 DOI:10.1016/j.aquatox.2024.107081

Elise Pesce , Jessica Benitez-Gonzalez , Andrew J. Tindall , Gregory F. Lemkine , Barbara Robin-Duchesne , Laurent M. Sachs , et David Du Pasquier

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引用次数: 0

摘要

干扰内分泌的化学品对野生动物和人类的影响备受关注。大量化学品已被证明会干扰脊椎动物的下丘脑-垂体-甲状腺轴（HPT）。对 HPT 轴的干扰，与雌激素轴、雄激素轴和类固醇生成（EATS）一样，是化学品监管中考虑的主要内分泌标准之一。针对这些问题，经济合作与发展组织（OECD）启动了涵盖 EATS 模式的测试指南（TGs）的验证工作。在甲状腺活性和/或干扰评估方面，经合组织有三项 TG 已通过验证，所有这些 TG 都使用了两栖动物。迄今为止，还没有基于鱼类的 OECD TG 用于检测甲状腺活性化学品 (TAC)。为了填补这一空白，我们开发了一种新的检测 TACs 的试验，即 TETHYS 试验（转基因刺五加胚胎甲状腺特异性试验）。该检测使用了一种在甲状腺球蛋白启动子控制下在甲状腺滤泡中表达绿色荧光蛋白的青鳉（Oryzias latipes）转基因品系Tg(tg:eGFP)。本研究测试了以下已知甲状腺激素系统作用机制的参考化学品：甲巯咪唑、高氯酸钠、四氟硼酸钠、双氯芬酸、碘帕酸、舒贝替罗、NH-3 和 1-850。除甲状腺受体拮抗剂外，所有测试的化学物质都具有甲状腺活性，可改变总荧光和甲状腺滤泡的大小。为了研究测试的特异性，我们测试了三种被认为对 HPT 轴无作用的化学物质：头孢呋辛、阿维菌素和 17α-炔雌醇。结果发现，这三种化学物质在 TETHYS 试验中均无活性。这种前景广阔的新方法可以作为制定新的经合组织技术指导文件的基础，用于对化学品的甲状腺活性进行监管评估。

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Testing the sensitivity of the medaka Transgenic Eleuthero-embryonic THYroid-Specific assay (TETHYS) to different mechanisms of action

There are many concerns about the impacts of Endocrine-Disrupting Chemicals on both wildlife and human populations. A plethora of chemicals have been shown to interfere with the Hypothalamic–Pituitary–Thyroid (HPT) axis in vertebrates. Disruption of the HPT axis is one of main endocrine criteria considered for the regulation of chemicals, along with the estrogen axis, androgen axis and steroidogenesis (EATS). In response to these concerns, the Organization for Economic Cooperation and Development (OECD) initiated the validation of test guidelines (TGs) covering the EATS modalities. Regarding thyroid activity and/or disruption assessment, three OECD TGs are validated, all of them using amphibians. To date, no OECD TGs based on fish are available for the detection of Thyroid Active Chemicals (TACs). To fill this gap, we developed a new test for the detection of TACs, the TETHYS assay (Transgenic Eleuthero-embryonic THYroid-Specific assay). This assay uses a medaka (Oryzias latipes) transgenic line Tg(tg:eGFP) expressing Green Fluorescent Protein in the thyroid follicles, under the control of the thyroglobulin promoter. This assay is performed at eleuthero-embryonic life-stages with an exposure length of 72 h. In the present study, the following reference chemicals with known thyroid hormone system mechanism of action have been tested: methimazole, sodium perchlorate, sodium tetrafluoroborate, diclofenac, iopanoic acid, sobetirome, NH-3 and 1–850. Except for the thyroid receptor antagonists, all chemicals tested were identified as thyroid active, modifying the total fluorescence and the size of the thyroid follicles. To investigate the test specificity, we tested three chemicals presumed to be inert on the HPT axis: cefuroxime, abamectin and 17α-ethinylestradiol. All were found to be inactive in the TETHYS assay. This promising New Approach Methodology can serve as a foundation for the development of a new OECD TG in the frame of regulatory assessment of chemicals for thyroid activity.

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来源期刊

Aquatic Toxicology 环境科学-毒理学

CiteScore

7.10

自引率

4.40%

发文量

250

审稿时长

56 days

期刊介绍： Aquatic Toxicology publishes significant contributions that increase the understanding of the impact of harmful substances (including natural and synthetic chemicals) on aquatic organisms and ecosystems. Aquatic Toxicology considers both laboratory and field studies with a focus on marine/ freshwater environments. We strive to attract high quality original scientific papers, critical reviews and expert opinion papers in the following areas: Effects of harmful substances on molecular, cellular, sub-organismal, organismal, population, community, and ecosystem level; Toxic Mechanisms; Genetic disturbances, transgenerational effects, behavioral and adaptive responses; Impacts of harmful substances on structure, function of and services provided by aquatic ecosystems; Mixture toxicity assessment; Statistical approaches to predict exposure to and hazards of contaminants The journal also considers manuscripts in other areas, such as the development of innovative concepts, approaches, and methodologies, which promote the wider application of toxicological datasets to the protection of aquatic environments and inform ecological risk assessments and decision making by relevant authorities.