Insights into organophosphorus insecticide malathion induced reproductive toxicity and intergenerational effect in zebrafish (Danio rerio)

The reproductive and transgenerational effects of malathion, a widely utilized low-toxicity organophosphorus insecticide, were explored using zebrafish as model animal. Adult zebrafish (F0) were exposed to malathion at 0.1-1.0 mg/L for 60 days for exploring the reproductive toxicity in sex differences and the potential mechanisms, and development and transcription levels in F1 offspring were assessed. Malathion significantly suppressed the fertility of zebrafish as evidenced by reduced spawning and lower fertilization rates in F1 offspring. Abnormal gonadal development and steroid hormone disorders were observed in F0 zebrafish, which was associated with the alterations in the transcription of core genes (such as cyp11a, cyp19a, vtg1, era) along the hypothalamus-pituitary-gonad-liver (HPGL) axis. The expression level of vtg1 played a key role in the malathion-induced sex dependence on E2 and VTG levels. The reduction of E2 and VTG could disrupt ovarian capability in females. E2 excess would cause feminization in males. Molecular docking indicated that reproductive disorders induced by malathion in zebrafish mainly through estrogen-like effects and CYP11A antagonism. Parental exposure to malathion abnormalized embryonic development in F1 offspring, comprising heartbeats decrease, deformities and body length reduction. Transcriptomics suggested that malathion-induced reproductive toxicity could be transmitted across generations, which may adversely affect fish populations.