Enantioselectivity of thyroid endocrine disruption caused by dinotefuran exposure in <i>Xenopus laevis</i> tadpoles

Dinotefuran, a chiral neonicotinoid pesticide, is known to cause endocrine disruption, but the specific impact of its enantiomers remains unclear. Xenopus laevis tadpoles were exposed to varying concentrations of <i>R-</i> and <i>S-</i>dinotefuran (0, 5, and 50 μg/L) for 21 days. Body length and developmental stages were measured, and hormone levels and HPT axis gene expression were analyzed. Molecular docking was performed to evaluate the activation of the thyroid hormone receptor (TRα) by the enantiomers. Dinotefuran exposure significantly decreased body length and delayed developmental stages, indicating developmental toxicity. It reduced T3, T4, and TSH levels, suggesting thyroid endocrine disruption. Dinotefuran increased the mRNA expression of TSH synthesis and receptor genes, likely compensating for lower T4. Changes in iodide uptake and deiodinase gene expression may explain reduced thyroid hormone levels. Molecular docking showed that both <i>R-</i> and <i>S-</i>dinotefuran can directly activate TRα. Additionally, enantioselective differences were observed at the gene expression level, indicating that the developmental toxicity and endocrine disruption effects of the dinotefuran enantiomers differ in their impact on HPT axis regulation. Dinotefuran altered HPT axis gene expression and thyroid hormone levels, causing thyroid endocrine disorders and delayed tadpole metamorphosis, posing a threat to frog populations.