Transgenerational Effects and Mechanisms of Tributyltin Exposure on Neurodevelopment in the Male Offspring of Rats

This study aimed to investigate the transgenerationaleffects oftributyltin exposure on rat neurodevelopment in male offspring andthe potential mechanisms. Neonatal female rats were exposed to theenvironmental level of tributyltin and then mated with nonexposedmales after sexual maturity to produce the F1 generation. The F1 generation(with primordial germ cell exposure) was mated with nonexposed malesto produce nonexposed offspring (the F2 and F3 generations). Neurodevelopmentalindicators and behavior were observed for the F1, F2, and F3 generationsduring postnatal days 1-25 and 35-56, respectively.We found premature eye-opening and delayed visual positioning in newbornF1 rats and anxiety and cognitive deficits in prepubertal F1 malerats. These neurodevelopmental impacts were also observed in F2 andF3 males. Additionally, F1-F3 males exhibited increased serotoninand dopamine levels and a loose arrangement of neurons in the hippocampus.We also observed a reduction in the expression of genes involved inintercellular adhesion and increased DNA methylation of the Dsc3 promoter in F1-F3 males. We concluded that tributyltinexposure led to transgenerational effects on neurodevelopment viaepigenetic reprogramming in male offspring. These findings provideinsights into the risks of neurodevelopmental disorders in offspringfrom parents exposed to tributyltin. Tributyltinexposure in rats increased the risk of neurodevelopmentaldisorders in male offspring over at least three generations.

Automated summary

This study investigated the transgenerational effects of tributyltin exposure on rat neurodevelopment in male offspring. The results showed adverse effects on neurodevelopment in F1, F2, and F3 generations, including premature eye-opening, delayed visual positioning, anxiety, cognitive deficits, loose arrangement of neurons in the hippocampus, increased serotonin and dopamine levels, and altered gene expression and DNA methylation patterns. These findings suggest that tributyltin exposure can lead to transgenerational neurodevelopmental disorders in male offspring via epigenetic reprogramming.