Abstract

Isoprothiolane exposure can affect early embryogenesis in zebrafish. • Isoprothiolane impairs cardiovascular development. • Transcriptomics revealed isoprothiolane inhibited Wnt signaling pathway. • BML-284 partially rescues isoprothiolane-induced developmental dysfunction. Isoprothiolane is a widely used organosulfur fungicide detected in surface waters worldwide at concentrations ranging from nanograms to micrograms per liter. However, its toxicological effects on vertebrates remain poorly understood. In this study, we used zebrafish to assess the developmental toxicity of isoprothiolane. Transgenic zebrafish lines Tg( myl7:GFP ) and Tg( fli1:GFP ) were exposed to isoprothiolane from 6 to 72 h post-fertilization (hpf). Early cardiovascular development and damage were assessed using H&E staining, immunofluorescence staining, and Western blot, while behavioral analysis evaluated locomotor activity. We observed dose-dependent cardiovascular toxicity, including pericardial edema, cardiac linearization, abnormal heart rate, reduced cardiomyocyte numbers, and impaired vascular branching, accompanied by inhibited cell proliferation and increased apoptosis. Transcriptomic analysis identified Wnt pathway suppression as a key mechanism underlying these defects. Furthermore, treatment with BML-284, a Wnt pathway agonist, partially rescued the cardiovascular defects and developmental abnormalities in zebrafish. Therefore, these findings reveal that isoprothiolane disrupts cardiovascular development through Wnt signaling inhibition, providing novel insights into fungicide-induced developmental toxicity and informing ecological risk assessment of organosulfur pesticides. Download: Download high-res image (191KB) Download: Download full-size image