Abstract：
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 (F0-F2) 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 µg/L DB79 decreased fecundity in the F0 and F1 generations by > 30 % and increased the condition factor of the F1 generation 1.24-fold. PPARα/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.
摘要：
溴化偶氮染料（BAD）分散蓝（DB79）是一种广泛存在的环境污染物。必须理解DB79的长期毒理学效应及其机制,以允许评估DB79污染的风险。采用硅片分析的双组学方法，生物信息学，和体外生物测定法用于研究环境相关浓度下DB79在斑马鱼中的跨代（F0-F2）毒性，并确定与DB79诱导的生育障碍相关的分子启动事件和关键事件。暴露于500µg/LDB79使F0和F1代的繁殖力降低了>30％，并使F1代的条件因子增加了1.24倍。发现PPARα/RXR和PXR配体结合激活是与繁殖力降低相关的关键分子启动事件。几个关键事件(脂肪酸氧化和摄取的变化，脂蛋白代谢，发现DB79通过使用双组学数据的生物信息学注释诱导了与脂质失调和异种生物的代谢和运输有关的）。阐明了由于BAD暴露导致斑马鱼跨代生育能力下降的生物分子基础，并确定了不良结果途径框架中的新生物分子靶标。这些结果将为未来的研究提供信息，并促进缓解战略的制定。
