Epigenetic biomarkers as tools for chemical hazard assessment: Gene expression profiling using the model Danio rerio

Recent reports raise the concern that exposure to several environmental chemicals may induce persistent changes that go beyond the exposed organisms, being transferred to subsequent generations even in the absence of the original chemical insult. These changes in subsequent non-exposed generations have been related to epigenetic changes. Although highly relevant for hazard and risk assessment, biomarkers of epigenetic modifications that can be associated with adversity, are still not integrated into hazard assessment frameworks. Here, in order to validate new biomarkers of epigenetic modifications in a popular animal model, zebrafish embryos were exposed to different concentrations of Bisphenol A (0.01, 0.1, 1 and 10 mg/L) and Valproic Acid (0.8, 4, 20 and 100 mg/L), two chemicals reported to alter the modulation of the epigenome. Morphological abnormalities and epigenetic changes were assessed at 80 hours-post fertilization, including DNA global methylation and gene expression of both DNA and histone epigenetic modifications. Gene expression changes were detected at concentrations below those inducing morphological abnormalities. These results further support the importance of combining epigenetic biomarkers with apical endpoints to improve guidelines for chemical testing and hazard assessment, and favour the integration of new biomarkers of epigenetic modifications into the standardized OECD test guideline 236 with zebrafish embryos.