Propisochlor disrupts cardiovascular and neural development through apoptotic and oxidative pathways in zebrafish

Propisochlor, a commonly used chloroacetanilide herbicide, is widely detected in aquatic environments; however, its developmental toxicity remains unclear. We used zebrafish embryos to examine the embryotoxic effects of sublethal propisochlor concentrations. Propisochlor significantly reduced the survival rate of the embryos and induced severe morphological deformities, including pericardial edema, reduced eye and head size, and shortened body length. Acridine orange and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining confirmed increased apoptosis. Mitochondrial respiration measurements revealed impaired basal respiration and ATP generation concurrent with reactive oxygen species overproduction and the activation of inflammatory mechanisms. Neurodevelopmental assessments using olig2:dsRed transgenic zebrafish showed markedly shortened dorsal and ventral motor axons and reduced neuronal network formation, which was supported by the downregulation of related genes. Cardiovascular toxicity assessments using cmlc2:dsRed and fli1a:EGFP transgenic lines revealed disrupted cerebrovascular development, defective aortic arch formation, impaired dorsal aorta-posterior cardinal vein separation, atrial enlargement, and reduced expression of cardiac developmental markers. Collectively, these findings indicate that propisochlor disrupts zebrafish embryogenesis by inducing apoptosis, mitochondrial dysfunction, oxidative stress, and inflammation, ultimately impairing neural, vascular, and cardiac development. This study highlights the potential ecological risk posed by propisochlor contamination during the early developmental stages.