Wang Aoxue, Liu Yuanyuan, Yan Yujia, Jiang Yuyao, Shi Shiyao, Wang Jie, Qiao Kun, Yang Long, Wang Shuting, Li Shuying, Gui Wenjun
Institute of Pesticide and Environmental Toxicology, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, P. R. China.
Research Centre for the Oceans and Human Health, City University of Hong Kong Shenzhen Research Institute, Shenzhen 518057, P. R. China.
Environ Sci Technol. 2025 Jan 14;59(1):142-151. doi: 10.1021/acs.est.4c07890. Epub 2024 Dec 24.
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 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) and thyroxine (T). 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 and T levels were reduced by 28% and 39.4%, respectively, compared to controls. Cotreatment with T 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. These findings suggest that CPF functions as a partial agonist of TRα, disrupting thyroid signaling and adversely affecting amphibian development.
毒死蜱（CPF）是一种广泛使用的有机磷杀虫剂，对水生动物具有严重的毒理学影响。尽管已对其神经毒性和内分泌干扰作用进行了广泛研究，但其对两栖动物变态的阶段特异性影响以及受体水平的相互作用仍不清楚。本研究调查了环境相关浓度（1.8和18μg/L）的CPF在关键发育阶段对变态的影响，终点包括变态前进展、甲状腺激素（TH）反应性基因表达以及三碘甲状腺原氨酸（T3）和甲状腺素（T4）水平。此外，采用分子对接、表面等离子体共振（SPR）和荧光素酶报告基因测定法来阐明CPF与甲状腺激素受体α（TRα）的相互作用。CPF加速了变态前发育并上调了TH反应性基因，但延迟了后期变态。与对照组相比，暴露于18μg/L CPF 21天后，T3和T4水平分别降低了28%和39.4%。T3与CPF共同处理减缓了蝌蚪发育，表明CPF以阶段依赖性方式影响甲状腺信号传导。CPF单独给药时与T3竞争TRα结合并刺激TRα介导的荧光素酶活性，但当CPF与T3共同暴露时该活性降低。这些发现表明CPF作为TRα的部分激动剂发挥作用，破坏甲状腺信号传导并对两栖动物发育产生不利影响。
