Exposure of Parental Zebrafish to Difenoconazole throughout Their Life Cycle May Lead to Developmental Toxicity in the F1 Generation through Epigenetic Changes in Gametes, Impaired Nutrient Supply from the Ovum, and Maternal Transfer of Difenoconazole

Abstract

Difenoconazole is a widely used agricultural fungicide that has been frequently detected in aquatic environments. Given its stable presence in aquatic environments, long-term exposure of wild fish may pose a risk to offspring embryonic development. This study demonstrated that exposure of zebrafish to environmental concentrations of difenoconazole throughout their life cycle resulted in abnormal development of offspring embryos/larvae, including decreased heart rate, delayed hatching, increased malformation rate, shortened body length, and increased mortality. These changes were significantly correlated with the affected apoptosis, autophagy, energy metabolism and MAPK signaling pathways in F1 generation. This transgenerational toxic effect results from epigenetic alterations in gametes, impaired nutrient supply from the ovum, and maternal transfer of difenoconazole. After exposure to difenoconazole, the development of female fish offspring was affected more than that of male fish offspring, which was mainly caused by the impaired nutrient supply from the ovum and the maternal transfer of difenoconazole. Because this transgenerational developmental toxicity was observed at environmental levels, difenoconazole may pose a threat to the survival of wild larvae and therefore a risk to wild fish populations.