Parental exposure to hexafluoropropylene oxide trimer acid induces transgenerational developmental toxicity and thyroid endocrine disruption effects in zebrafish

作者：Xiaohui Zhao, Dan Yang, Jorke H. Kamstra, Shasha Dong, Jianhui Xu, Xiaohui Li, Dezhi Chen, Yawei Shi, Ya Sun, Guanghui Ding · 发表于：Ecotoxicology and Environmental Safety · 年份：2025 · DOI：10.1016/j.ecoenv.2025.119476 · 被引用次数：2 · 研究领域：Per- and polyfluoroalkyl substances research、Fluoride Effects and Removal、Effects and risks of endocrine disrupting chemicals

Hexafluoropropylene oxide trimer acid (HFPO-TA), a novel alternative to perfluorooctanoic acid, has been ubiquitously detected in aquatic environment. However, the current understanding of its transgenerational toxicity in fish and the underlying mechanisms remains scarce. Therefore, in this study, adult zebrafish (F0) were exposed to HFPO-TA at concentrations of 0, 0.5, 5, and 50 μg/L for 90 days, and transgenerational developmental toxicity and thyroid disruption effects across three generations were investigated. The results revealed that parental HFPO-TA exposure induced significant reductions of the heart rate and swirl-escape rate in unexposed F1 and F2 offspring, which could be induced by dysregulating genes involved in the central nervous system development and associated with the thyroid hormone (TH) disorders. Furthermore, histological changes of thyroid follicles, disruptions of TH homeostasis and transcriptional expressions of key genes involved in the hypothalamic-pituitary-thyroid axis, and DNA methylation modifications in the promoter of two key genes, were observed across three generations. These suggested that parental HFPO-TA exposure could dysregulate the gene expressions via disrupting DNA methylation in the promoters, and consequently induced the adverse effects. Interestingly, the thyroid disruption effects in F1 offspring were associated with maternal transfer of HFPO-TA and promoter methylation of key genes, while the adverse effects in F2 offspring we...