Chlorpyrifos Influences Tadpole Development by Disrupting Thyroid Hormone Signaling Pathways

作者：Aoxue Wang, Yuanyuan Liu, Yujia Yan, Yuyao Jiang, Shiyao Shi, Jie Wang, Kun Qiao, Yang Long, Shuting Wang, Shuying Li, Wenjun Gui · 发表于：Environmental Science & Technology · 年份：2024 · DOI：10.1021/acs.est.4c07890 · 被引用次数：10 · 研究领域：Environmental Toxicology and Ecotoxicology、Pesticide and Herbicide Environmental Studies、Toxic Organic Pollutants Impact

Chlorpyrifos (CPF) is a widely used organophosphate insecticide with serious toxicological effects on aquatic animals. Although extensively studied for neurotoxicity and endocrine disruption, its stage-specific effects on amphibian metamorphosis and receptor-level interactions remain unclear. This study investigated the effects of CPF on Xenopus laevis metamorphosis at environmentally relevant concentrations (1.8 and 18 μg/L) across key developmental stages, with end points including premetamorphic progression, thyroid hormone (TH)-responsive gene expression, and levels of triiodothyronine (T 3 ) and thyroxine (T 4 ). Additionally, molecular docking, surface plasmon resonance (SPR), and luciferase reporter gene assays were employed to elucidate CPF’s interaction with the thyroid hormone receptor alpha (TRα). CPF accelerated premetamorphic development and upregulated TH-responsive genes but delayed later-stage metamorphosis. After 21 days of exposure to 18 μg/L CPF, T 3 and T 4 levels were reduced by 28% and 39.4%, respectively, compared to controls. Cotreatment with T 3 and CPF slowed tadpole development, indicating that CPF affects thyroid signaling in a stage-dependent manner. CPF competed with T3 for TRα binding and stimulated TRα-mediated luciferase activity when administered alone, but this activity decreased when CPF was coexposed to T 3 . These findings suggest that CPF functions as a partial agonist of TRα, disrupting thyroid signaling and adversely affecting amphibia...