Chlorpyrifos Influences\nTadpole Development by Disrupting\nThyroid Hormone Signaling Pathways

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