Myclobutanil induces cardiovascular toxicity via thyroid disruption in zebrafish larvae.

Myclobutanil (MYC), a widely used triazole fungicide, is extensively employed in agriculture. MYC residues are frequently found in ecosystems and living organisms. Nevertheless, research on its potential adverse effects on embryonic development remains limited. In this study, zebrafish embryos were exposed to MYC (0, 0.5 and 1 mg/L) between 4 and 96 h post fertilization (hpf) to evaluate the cardiovascular toxicity and molecular mechanisms. The results demonstrated that MYC decreased the survival and hatching rate, and heart rate, but increased the malformation rate and spontaneous movement. MYC caused aberrant cardiovascular morphology and function in the myl7:egfp and fli1:egfp zebrafish, as well as dysregulated expression of cardiovascular developmental genes. Simultaneously, MYC also disrupted thyroid hormone homeostasis and modified the expression of hypothalamus-pituitary-thyroid (HPT) axis-related genes. Molecular docking analysis revealed that MYC exhibited robust binding affinity to the catalytic residues of thyroid hormone receptor β. Notably, T3 supplementation could significantly ameliorated these adverse toxicities, indicating thyroid hormone disruption as a key mechanism underlying MYC-induced cardiovascular defects. Overall, our study demonstrated MYC-induced cardiovascular toxicity and identified the underlying mechanisms of thyroid hormone disruption through competitive binding to the TRβ ligand-binding domain in zebrafish.