Intergenerational effects of parental dimefluthrin and microcystins co-exposure on zebrafish: Impaired embryonic and larval development

Abstract

Dimefluthrin (DIM), a widely used pyrethroid insecticide, and microcystin-LR (MC-LR), a potent cyanotoxin produced by harmful algal blooms, are both frequently detected in aquatic environments. However, the potential combined effects of these two contaminants, particularly regarding intergenerational toxicity, remain largely unexplored. In this study, we aimed to evaluate the intergenerational effects of chronic parental co-exposure to DIM and MC-LR in zebrafish. Adult zebrafish were exposed to DIM and MC-LR, alone or in combination, for 160 days. A panel of phenotypic, histological, biochemical, and transcriptomic analyses were conducted in both adults and their F1 offspring. Chronic co-exposure resulted in ovarian and hepatic tissue damage and reduced spawning rates in adult zebrafish. In the F1 generation, significant developmental abnormalities were observed, including reduced heart rate, spinal curvature, and impaired swim bladder inflation. These phenotypic defects were accompanied by significant downregulation of the mesothelial markers anxa5b and hprt1l, both of which contribute to swim bladder development in F1 larvae. Transcriptomic analysis revealed enrichment of ferroptosis-related pathways in maternal ovaries and both ferroptosis and necroptosis pathways in F1 larvae. Furthermore, mouse double minute 2 homolog (MDM2), fatty acid synthase (FASN), and farnesoid X receptor (FXR) were identified through molecular docking as potential DIM-interacting targets implicated in the regulation of ferroptosis. These findings provide new insights into the multigenerational risks posed by co-exposure to environmental pesticides and cyanotoxins, and emphasize the importance of incorporating intergenerational effects into water quality guidelines and chemical management strategies.