Intergenerational reproductive toxicity of parental exposure to prothioconazole and its metabolite on offspring and epigenetic regulation associated with DNA methylation in zebrafish.

[Display omitted] • Environmentally relevant levels of PTC and dPTC reduced the fecundity of F0 parental zebrafish, especially in female zebrafish. • Transgenerational abnormal development occurred in unexposed offspring. • The possible mechanism was related to epigenetic modification involving DNA methylation. Prothioconazole (PTC) is a widely used agricultural fungicide, and its parent and metabolite prothioconazole-desthio (dPTC) have been detected in diverse environmental media. This study was aimed at investigating the gender-dependent effects on adult zebrafish reproduction and intergenerational effects on offspring development following parental exposure to PTC and dPTC. The results showed that after the adult zebrafish (F0) was exposed to 0.5 and 10 μg/L PTC and dPTC for 21 days, the fertility and gametogenesis of female zebrafish were decreased more significantly than that of male zebrafish. After that, three fecundity tests were conducted in the exposure period to explore the development endpoints of F1 embryos/larvae without further treatment with PTC and dPTC exposure. However, PTC and dPTC exposure did lead to abnormal development of F1 embryos, including delayed hatching, shortened body length, abnormal development and significant changes in locomotor behavior. These changes were related to the abnormal expression of sex hormones and the regulation of DNA methylation in F0 fish. In a word, the results of this study showed that parental PTC and dPTC interference have sex-dependent reproductive toxicity on F0 zebrafish, which may be passed on to the next generation through epigenetic modification involving DNA methylation, resulting in alternations in growth phenotype of offspring. [ABSTRACT FROM AUTHOR]