Integrated approach of eco-epigenetics and eco-metabolomics on the stress response of bisphenol-A exposure in the aquatic midge Chironomus riparius

The stress response mechanisms of Bisphenol A (BPA), an endocrine disrupting compound, remain to be elucidated. In this study, we explored the effects of BPA on the non-biting midge Chironomus riparius through basic ecotoxicity assays, DNA damage (comet assay), eco-epigenetics (global DNA and histone methylations) and non-targeted global metabolomics (NMR based) approaches. The reproduction failure, increase in DNA damage, global DNA hyper-methylation, and increased global histone modification (H3K36) status were evident due to BPA exposure at 10% lethal concentration (LC₁₀: 1 mg/L, based on 48 h acute toxicity). Moreover, non-targeted global metabolomics followed by pathway analysis identified alterations of energy metabolism, amino acids, and methionine metabolisms etc. Most importantly, we found a potential cross-talk between altered epigenetics and metabolites, such as, increase in methionine and o-phosphocholine metabolites corresponds with the phenomena of global hyper-methylation in DNA and H3K36 mark. Overall, our results suggests that the crosstalk of global metabolomics and epigenetic modification was fundamental of the underlying mechanisms in BPA-induced stress response in C. riparius.