Investigating multigenerational epigenetic adaptation of the hepatic wound-healing response

The possibility that ancestral environmental conditions and exposures could result in effects inherited across generations, with potential impact for human health, has been long debated. Here, we comprehensively investigate transgenerational effects of the hepatotoxicant carbon tetrachloride (CCl4) on the hepatic wound-healing response in male rats. Detailed microscopic and clinical pathology evaluations do not support adaptive phenotypic suppression of the hepatic wound-healing response or a greater fitness of animals with ancestral liver injury exposure as originally reported. We produced RNAseq libraries on the F2 liver samples to further characterize any adaptive effect based on molecular changes.祖先所处的环境条件与暴露史可引发跨代遗传的效应，并对人类健康存在潜在影响——这一可能性长期以来饱受学界争议。本研究针对肝毒性物质四氯化碳（carbon tetrachloride，CCl4）对雄性大鼠肝脏创伤愈合反应的跨代遗传效应展开全面探究。细致的显微评估与临床病理学评估结果显示，既未观测到肝脏创伤愈合反应存在适应性表型抑制现象，也未如最初报道那般，发现祖先暴露于肝损伤环境的动物具备更强的生存适应性。我们对F2代大鼠的肝脏样本构建了RNA测序（RNAseq）文库，以期基于分子层面的变化进一步阐明潜在的适应性效应。