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<p>As an alternative to perfluorooctanoic acid, hexafluoropropylene oxide trimer acid (HFPO-TA) has become a widespread environmental contaminant, posing potential risks to aquatic organisms. However, its intergenerational reproductive toxicity in fish remains poorly understood. In this study, following a 90-d exposure of four-month-old zebrafish to HFPO-TA (0.5, 5, and 50 µg/L), subsequent generation was reared in clean water until adulthood to assess intergenerational reproductive effects. Results revealed that parental HFPO-TA exposure inhibited gonadal development in both generations and affected F1 offspring development. A female-skewed sex ratio was observed in unexposed F1 offspring, accompanied by the dysregulation of genes involved in sex differentiation and maintenance. Furthermore, transcriptions of key genes along the hypothalamus-pituitary-gonad-liver axis were dysregulated across two generations, leading to disorders of sex hormone and vitellogenin levels, and ultimately resulting in intergenerational reproductive dysfunction. It was found that the HFPO-TA exposure also induced DNA hypermethylation in gonads across two generations, which could contribute to the observed reproductive toxicity. Overall, this study provides evidence for the intergenerational reproductive toxicity of HFPO-TA in zebrafish, with potential adverse implications for the sustainability of fish populations.</p>

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Parental HFPO-TA exposure induces intergenerational reproductive toxicity and DNA methylation alterations in zebrafish

  • 期刊论文

  • 发表日期：

    2026年1月20日

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  • Shasha Dong,
  • Xiaohui Zhao,
  • Xuan Ren,
  • Jing Zhang,
  • Zhibo Liu,
  • Dan Yang,
  • Ning Ji,
  • Yawei Shi,
  • Ya Sun,
  • Guanghui Ding

摘要

As an alternative to perfluorooctanoic acid, hexafluoropropylene oxide trimer acid (HFPO-TA) has become a widespread environmental contaminant, posing potential risks to aquatic organisms. However, its intergenerational reproductive toxicity in fish remains poorly understood. In this study, following a 90-d exposure of four-month-old zebrafish to HFPO-TA (0.5, 5, and 50 µg/L), subsequent generation was reared in clean water until adulthood to assess intergenerational reproductive effects. Results revealed that parental HFPO-TA exposure inhibited gonadal development in both generations and affected F1 offspring development. A female-skewed sex ratio was observed in unexposed F1 offspring, accompanied by the dysregulation of genes involved in sex differentiation and maintenance. Furthermore, transcriptions of key genes along the hypothalamus-pituitary-gonad-liver axis were dysregulated across two generations, leading to disorders of sex hormone and vitellogenin levels, and ultimately resulting in intergenerational reproductive dysfunction. It was found that the HFPO-TA exposure also induced DNA hypermethylation in gonads across two generations, which could contribute to the observed reproductive toxicity. Overall, this study provides evidence for the intergenerational reproductive toxicity of HFPO-TA in zebrafish, with potential adverse implications for the sustainability of fish populations.