Chronic toxic effects of isoflucypram on reproduction and intestinal energy metabolism in zebrafish (Danio rerio)

The intestine is a vital organ involved in chemical and nutrient uptake and biotransformation. Intestinal dysfunction can impair energy and material supply for reproduction. Isoflucypram, a new succinate dehydrogenase inhibitor fungicide, is highly toxic to aquatic systems. However, the chronic toxic effects of isoflucypram on intestinal differentiation in aquatic organisms remain unknown. In this study, zebrafish (F0, 4-month-old) were exposed to 0, 0.008, or 0.08 μM isoflucypram for 120 days. After 90 days of exposure, F0 generations of adult zebrafish were paired, and the corresponding F1 generation embryos were obtained and observed. After 120 days of exposure, the gut of F0 generation zebrafish was collected, and intestinal histopathology and mitochondrial morphology were analyzed. Exposure to 0.08 μM isoflucypram resulted in significant death, hatching delay, and malformation (blood clot clustering, pericardial edema, and microphthalmia) of F1 embryos and larvae. Exposure to isoflucypram caused irregular and swollen villi in the zebrafish gut, accompanied by alterations in the intestinal mitochondrial ultrastructure. In addition, the differentially expressed genes involved in mitochondrial energy metabolism were significantly enriched. Overall, our data suggest that chronic exposure to isoflucypram is associated with reproductive and intestinal dysfunction in adult zebrafish.