The anti-lipidemic drug simvastatin modulates Epigenetic Biomarkers in the Amphipod Gammarus locusta

The adverse effects of certain environmental chemicals have been recently associated with epigenome modulation. Although the changes in the epigenetic signature are still not integrated into hazard and risk assessment, they are interesting candidates for linking environmental exposures to altered phenotypes given that these changes may be passed across multiple non-exposed generations. Here, we addressed the effects of simvastatin (SIM), one of the most prescribed human pharmaceuticals, in epigenetic regulators of the amphipod Gammarus locusta, as a proxy to support its integration in hazard and environmental risk assessment. SIM is a known modulator of epigenome in mammalian cell lines, and has been reported to impact G. locusta ecological endpoints at environmentally relevant levels. G. locusta juveniles were exposed to three SIM concentrations (0.32, 1.6 and 8 μg.L-1), for 15 days. The basal expression of selected epigenetic regulators was determined, along with the quantification of DNA methylation levels and the assessment of key ecological endpoints. Exposure to 0.32 and 8 μg.L-1 SIM induced significant downregulation of DNA methyltransferase1 (dnmt1), concomitantly with Global DNA hypomethylation and impact on growth. Overall, this work is the first to validate the basal expression of key epigenetic regulators in a keystone marine crustacean, supporting the integration of epigenetic biomarkers into hazard assessment frameworks.