Tributyltin causes generational neurodevelopmental toxicity and the protective effect of folic acid in zebrafish

Tributyltin (TBT), a common organotin environmental pollutant, may pose a threat to human development during critical early-life periods. We aimed to assess the neurodevelopmental intergenerational toxicity of early-life exposure to TBT and the protective effect of DNA methyl donor folic acid (FA). Specifically, after early-life exposure (1-21 days post-fertilization, dpf) to TBT (0, 1, 10 and 100 ng/L), zebrafish (Danio rerio) were cultured in clean medium until sexual maturity. The exposed females were mated with unexposed males to produce embryos (F1). The F1 generation were cultured (4-120 hours post-fertilization, hpf) with and without 1 mmol/L FA. The neurotoxic effects of early-life TBT exposure for zebrafish and their offspring (F1) were significantly enhanced anxiety and reduced aggression, decreased gene expression of DNA methyltransferase in the brain and increased serotonin levels in the body. Moreover, the intergenerational neurodevelopmental toxicity, as manifested in the F1 generation, was attenuated by FA supplementation. In summary, early-life TBT exposure led to intergenerational neurodevelopmental deficits in zebrafish, and DNA methyl donors had a protective effect on F1 neurodevelopment, which can inform the prevention and treatment of intergenerational neurotoxicity due to organotin pollutants.