Combining transcriptomics and metabolomics to assess neurodevelopmental alteration caused by in utero exposure of mice to three putative thyroid hormone system disruptors

IF 4.8 3区医学 Q1 PHARMACOLOGY & PHARMACY

Toxicology Pub Date : 2024-08-11 DOI:10.1016/j.tox.2024.153905

引用次数: 0

Abstract

Gestating mice were exposed to three chemicals, tetrabromo-bisphenol A (TBBPA; 2 mg/kg/day), amitrole (25 and 50 mg/kg/day) and pyraclostrobin (0.4 and 2 mg/kg/day) to assess their capacity to act as thyroid hormone disruptors and compromise neurodevelopment. Propyl-thio-uracyl, a known pharmacological inhibitor of thyroid gland secretion, was used at both high and low dose as a reference thyroid hormone system disruptor (1 ppm, 1500 ppm). A combination of plasma metabolomics and striatum transcriptomics revealed the induced change in pups at the postnatal stages. Although the underlying mechanism is unlikely to involve thyroid hormone disruption, these chemicals had a detectable effect on pups’ neurodevelopment.

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结合转录组学和代谢组学评估小鼠在子宫内暴露于三种假定的甲状腺激素系统干扰物所导致的神经发育改变。

妊娠小鼠暴露于四溴双酚 A（TBBPA；2 毫克/千克/天）、双甲脒（25 和 50 毫克/千克/天）和吡唑醚菌酯（0.4 和 2 毫克/千克/天）这三种化学物质，以评估它们作为甲状腺激素干扰物和损害神经发育的能力。丙基硫脲是一种已知的甲状腺分泌药理抑制剂，以高剂量和低剂量作为甲状腺激素干扰物的参考（1 ppm、1500 ppm）。结合血浆代谢组学和纹状体转录组学发现了幼鼠在出生后阶段的诱导变化。虽然其根本机制不太可能涉及甲状腺激素干扰，但这些化学物质对幼崽的神经发育有可检测到的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology 医学-毒理学

CiteScore

7.80

自引率

4.40%

发文量

222

审稿时长

23 days

期刊介绍： Toxicology is an international, peer-reviewed journal that publishes only the highest quality original scientific research and critical reviews describing hypothesis-based investigations into mechanisms of toxicity associated with exposures to xenobiotic chemicals, particularly as it relates to human health. In this respect "mechanisms" is defined on both the macro (e.g. physiological, biological, kinetic, species, sex, etc.) and molecular (genomic, transcriptomic, metabolic, etc.) scale. Emphasis is placed on findings that identify novel hazards and that can be extrapolated to exposures and mechanisms that are relevant to estimating human risk. Toxicology also publishes brief communications, personal commentaries and opinion articles, as well as concise expert reviews on contemporary topics. All research and review articles published in Toxicology are subject to rigorous peer review. Authors are asked to contact the Editor-in-Chief prior to submitting review articles or commentaries for consideration for publication in Toxicology.