AhR Mediates the Neurodevelopmental Toxicity of PFOSA in Zebrafish Larvae

Perfluorooctane sulfonamide (PFOSA), the direct precursor to perfluorooctane sul-fonate (PFOS), is widely presented in the environment. Research has indicated that PFOSA is cardiotoxic and hepatotoxic, but its impact on neurodevelopment remains unclear. In the current study, we observed that exposure of PFOSA caused neurode-velopmental toxicity in zebrafish embryos in a dose-dependent manner, as evidenced by impaired motor abilities and decreased swimming distance. We then demonstrated that PFOSA exposure downregulated the mRNA expression of neurodevelopment-related genes including a1-tubulin, elavl3, ache and dat. Moreover, PFOSA exposure resulted in dose-dependent oxidative stress, which triggers apoptosis in the brains of zebrafish larvae. We further showed that inhibition of the aryl hydrocarbon receptor (AhR) alle-viated the oxidative stress and apoptosis induced by PFOSA-induced, thereby coun-teracting the neurodevelopmental abnormalities in zebrafish larvae. In conclusion, these findings indicate PFOSA causes neurodevelopmental disorders by inducing oxi-dative stress and apoptosis through the AhR pathway.