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

Abstract

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.

Graphical abstract

Keywords

Hexafluoropropylene oxide trimer acid / Intergenerational reproductive toxicity / DNA methylation / Hypothalamus-pituitary-gonad-liver axis / Zebrafish

Highlight

	● HFPO-TA exposure inhibited the gonadal development in two generations of zebrafish.
	● HFPO-TA exposure induced the feminization in F1 offspring.
	● HFPO-TA induced intergenerational reproductive toxicity by disrupting the HPGL axis.
	● Global DNA hypermethylation occurred in gonads across two generations of zebrafish.

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