Shenggan Wu, Xuehua An, Ting Xu, Dou Wang, Zhenlan Xu, Yuanxiang Jin, Xinquan Wang*, Yun Li*, Yanhua Wang*

Journal of Hazardous Materials；2026

Abstract: 

As an emerging alternative to perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimeric acid (HFPO-TA) has attracted increasing attention due to its widespread environmental occurrence and strong propensity for bioaccumulation. Nevertheless, the reproductive toxicity of PFOA and HFPO-TA in aquatic animals, as well as their effects on subsequent generations, remains poorly understood. To elucidate the reproductive effects of these compounds, adult male and female zebrafish were exposed to PFOA or HFPO-TA at concentrations of 0.5 and 50 µg/L, after which offspring were generated and collected for subsequent analyses. The findings demonstrated that both compounds disrupted mitochondrial integrity in gonadal cells, induced endocrine disturbances, altered sex hormone levels, and caused abnormal gonadal cell development, collectively impairing reproductive function. HFPO-TA elicited more severe endocrine disruption and gonadal damage in parental zebrafish than PFOA, with females exhibiting greater susceptibility to endocrine perturbation. In the offspring larvae, profound transcriptomic reprogramming was observed, concomitant with disturbances in growth and development, redox homeostasis, apoptotic signaling, and swimming performance. Notably, PFOA exerted stronger intergenerational toxicity, affecting offspring more profoundly than HFPO-TA. In summary, while HFPO-TA produced a more pronounced reproductive toxicity phenotype in parental zebrafish, PFOA posed a substantially greater risk to future generations.