Intergenerational toxic effects of parental exposure to bisphenol AF on offspring and epigenetic modulations in zebrafish

Abstract

Bisphenol AF (BPAF), an endocrine-disrupting chemical, has been detected in various environmental media because of its wide industrial applications. Meanwhile, substances that are known to be toxic to the reproductive system have been observed to interfere with the development of the offspring following parental exposure. This study was aimed at determining the gender-dependent intergenerational effects of BPAF on offspring development following either paternal or maternal exposure of adult zebrafish to an environmental concentration of BPAF. Four-month-old zebrafish (F0) were exposed to 10 μg/L of BPAF for 28 days, the developmental endpoints of F1 embryos were then tested without further treatment with BPAF. The results show that paternal BPAF exposure decreased the hatching rate, increased mortality, and shortened the body lengths of F1 larval offspring. In addition, it changed DNA and m⁶A RNA methylation gene expression levels in F0 testes and F1 larvae. Although maternal exposure increased mortality and enhanced antioxidant enzyme activities in F1 larvae, only DNA methylation gene expression was altered in F0 ovaries and F1 larvae. In addition, a short term BPAF exposure of zebrafish embryos from 4 h post-fertilization (hpf) until 120 hpf similarly impaired the early development of the larvae but only at a level relatively higher than 10 μg/L; and DNA and RNA methylation gene expression was regulated to some extent in BPAF exposure groups. Overall, our results indicate the gender-specific effects of BPAF on offspring development and epigenetic modulations, suggesting a relatively high susceptibility within the exposure window during gametogenesis and early embryonic developmental stages to environmental chemicals.

Keywords: DNA methylation; Environmental endocrine disrupting chemical; Offspring development; RNA methylation; Zebrafish.