Chlorpyrifos Influences Tadpole Development by Disrupting Thyroid Hormone Signaling Pathways

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 mu g/L) across key developmental stages, with end points including premetamorphic progression, thyroid hormone (TH)-responsive gene expression, and levels of triiodothyronine (T3) and thyroxine (T4). 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 (TR alpha). CPF accelerated premetamorphic development and upregulated TH-responsive genes but delayed later-stage metamorphosis. After 21 days of exposure to 18 mu g/L CPF, T3 and T4 levels were reduced by 28% and 39.4%, respectively, compared to controls. Cotreatment with T3 and CPF slowed tadpole development, indicating that CPF affects thyroid signaling in a stage-dependent manner. CPF competed with T3 for TR alpha binding and stimulated TR alpha-mediated luciferase activity when administered alone, but this activity decreased when CPF was coexposed to T3. These findings suggest that CPF functions as a partial agonist of TR alpha, disrupting thyroid signaling and adversely affecting amphibian development.