Transgenerational neurotoxic effects of triphenyltin on marine medaka: Impaired dopaminergic system function

Triphenyltin (TPT), a widely used environmental contaminant in antifouling paints, is known for its neurotoxic effects. To investigate the multigenerational impacts of long-term exposure (6 weeks) to environmental concentrations of TPT (100 ng/L) on either parent, we performed mixed mating between control and exposed groups (males or females). Although there was no direct contact with TPT in the subsequent generations, both the first and second generations displayed behavioral abnormalities, including reduced activity and impaired cognitive function, with pronounced gender differences and anxiety-like behaviors. Females were more susceptible than males, displaying a significantly increased time spent in the mirror-proximal zone in both F1 and F2 generations. Additionally, F0 females exhibited a marked reduction in the time spent in the bright area, further supporting the role of sex differences in behavioral responses. Notably, the maternal contribution of marine medaka (Oryzias melastigma) played a more significant role in the inheritance of TPT-induced cognitive deficits. A reduction in DA levels and AChE activity was observed across generations, regardless of gender, underscoring the critical role of DA-AChE balance in maintaining cognitive function. Additionally, gender differences and the hereditary effects of TPT exposure on anxiety-like behaviors were strongly associated with the transcriptional regulation of pparγ and gst. Impaired transcription of key genes in the dopaminergic system resulted in reduced DA levels, with the intergenerational transmission of mao being closely linked to behavioral impairments. In summary, TPT-induced neurotoxicity presents both hereditary effects and gender-specific differences, emphasizing the maternal influence in the inheritance of cognitive abilities and shedding light on the genetic impact of parental exposure.