Epigenetic mechanisms of DNA methylation in the transgenerational effect of ethylhexyl salicylate on zebrafish

In this study, a 120-day whole-life cycle exposure and oviposition experiment on zebrafish with maternal and paternal mixed mating strategy was conducted to investigate the epigenetic mechanism of DNA methylation in ethylhexyl salicylate (EHS, 1, 10, 100 μg/L)-induced transgenerational effects. Results showed that EHS could induce the decrease of DNA methyltransferase 1 (DNMT1) activity and average global DNA methylation level in maternal parents and the increase of the above indexes in paternal parents, while the change of glycine N-methyltransferase activity was opposite to DNMT1. The average global DNA methylation levels were significantly increased in the offsprings of both parents exposed and father-only exposed to EHS, suggesting that EHS-induced epigenetic modifications may be stable and heritable. Hierarchical clustering analysis of promoter at different methylation sites showed that the DNA methylation pattern of offsprings were similar to that of the paternal parents, meaning that the offsprings may have inherited paternal DNA methylation pattern with eya2, pcdh2g5 and pcdh2g1 as key genes and lead to high locomotor activity in offsprings. KEGG pathway analysis showed that parental exposure to EHS may interfere with the central nervous system, insulin function system, melanogenesis system and the normal development of somatic axis of offsprings.