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. Overall design: Treatment of three generations of Sprague Dawley rats.Treatment of F0 and F1 with either 100% olive oil or 50% (v/v) CCl4 in olive oil via oral gavage three times a week for 6 weeks followed by 2 weeks recovery before mating. Treatment of F2 with either 100% olive oil, 8% (v/v) CCl4 in olive oil or 50% (v/v) CCl4 in olive oil via oral gavage three times a week for 6 weeks; sampling of liver after 39 days. Isolation of total RNA from rat liver tissue, n=7 per group, 12 different treatment conditions (F0-control/F1-control/F2-control, F0-control/F1-control/F2-treated_CCl4_8%, F0-control/F1-control/F2-treated_CCl4_50%, F0-control/F1-treated/F2-control, F0-control/F1-treated/F2-treated_CCl4_8%, F0-control/F1-treated/F2-treated_CCl4_50%, F0-treated/F1-control/F2-control, F0-treated/F1-control/F2-treated_CCl4_8%, F0-treated/F1-control/F2-treated_CCl4_50%, F0-treated/F1-treated/F2-control, F0-treated/F1-treated/F2-treated_CCl4_8%, F0-treated/F1-treated/F2-treated_CCl4_50%)