Maternal exposure to fipronil results in sulfone metabolite enrichment and transgenerational toxicity in zebrafish offspring: Indication for an overlooked risk in maternal transfer?

Ecotoxicological studies show the association between pesticide pollution and transgenerational toxicity in aquatic organisms. However, a less considered risk is that many pesticides can be metabolized and transferred to offspring as new toxicants. In this study, we used zebrafish to evaluate the maternal transfer risk of fipronil (FIP), which is a great threat to aquatic organisms with toxic metabolite formation. After 28-day exposure to environmentally relevant concentrations (1.0, 5.0 and 10.0 μg/L) of FIP in adult female zebrafish (F0), the toxicants off-loading and transgenerational toxicity in offspring were studied. High burdens of FIP and its sulfone metabolite were found in both F0 and the embryos (F1), resulting in increased CYP450 activity. The residual levels of the metabolite were higher than those of the parent compound. Chiral analysis further showed a preferential accumulation of S-enantiomer of FIP in both F0 and F1. Maternal exposure to FIP increased the malformation rate and decreased the swim speed in larvae. Additionally, after exposure, the levels of thyroid hormones (THs), including triiodothyronine (T3) and thyroxine (T4), decreased in both generations, particularly in the F1. Gene transcription expression along the hypothalamic-pituitary-thyroid (HPT) axis was also significantly affected. Maternal exposure to FIP increased sulfone metabolite enrichment and cause multiple toxic effects in F1. Findings from this study highlight the key role of biologically active product formation in the maternal transfer of pollutants and associated risk assessment.