Multigenerational effects of disperse blue 79 at environmentally relevant concentrations on zebrafish (Danio rerio) fecundity: An integrated approach

The brominated azo dye (BAD) Disperse Blue (DB79) is a widespread environmental pollutant. The long-term toxicological effects of DB79 and the mechanisms thereof must be understood to allow assessment of the risks of DB79 pollution. A dual-omics approach employing in silico analysis, bioinformatics, and in vitro bioassays was used to investigate the transgenerational (F-0-F-2) toxicity of DB79 in zebrafish at environmentally relevant concentrations and identify molecular initiating events and key events associated with DB79-induced fertility disorders. Exposure to 500 mu g/L DB79 decreased fecundity in the F-0 and F-1 generations by > 30 % and increased the condition factor of the F-1 generation 1.24-fold. PPAR alpha/RXR and PXR ligand binding activation were found to be critical molecular initiating events associated with the decrease in fecundity. Several key events (changes in fatty acid oxidation and uptake, lipoprotein metabolism, and xenobiotic metabolism and transport) involved in lipid dysregulation and xenobiotic disposition were found to be induced by DB79 through bioinformatic annotation using dual-omics data. The biomolecular underpinnings of decreased transgenerational fertility in zebrafish attributable to BAD exposure were elucidated and novel biomolecular targets in the adverse outcome pathway framework were identified. These results will inform future studies and facilitate the development of mitigation strategies.