Laura Sabater, NFRG PhD student, gave an excellent presentation at NEPG 2017 - October 30th, 2017

Laura has brought pride to NFRG thanks to an outstanding presentation entitled "Protective heritable reprogramming of hepatic wound healing in liver fibrosis" at North-East Postgraduate Conference 2017, held in Newcastle on October 30th.

Background: In addition to genetic adjustment to environmental insults, there is also an adaptive, epigenetic mechanism that generates heritable adaptation in wound healing during liver fibrosis in male rats. The adapted rats show significant reduction in fibrogenesis. We were interested to discover if this adaptive mechanism was transient or whether it persists through the lifetime of the adapted animal. We also asked whether ancestral liver damage leads to heritable reprogramming of hepatic wound healing via female lineage.

Methods: We established CCl4-induced fibrosis in outbred male rats in F0, then allowed the animals to fully resolve fibrosis prior to breeding. Another group of rats was left for 100 days to achieve full sperm turnover to delineate whether the adaptation was transient or permanent. Male offspring (F1) were injured in the same way and the process repeated to produce a third generation (F2) which were again subject to CCl4 injury. All combinations of injured parents/grandparents were used to produce offspring from males injured in one or both generations. Females (F1) from injured and control lineage were bred and their male offspring was also subjected to CCl4 injury.

Results: Histological analysis revealed that relative to controls, male offspring of rats with ancestral liver damage had lower collagen deposition in the fibrotic livers. No changes in the degree of tissue injury or inflammation were observed between generations. In contrary, no differences in the collagen deposition were found in the female offspring.

Discussion: Adapted animals from male lineage were protected from developing severe fibrosis. No changes in tissue injury or inflammation show that adaptation was selectively directed at the wound healing/fibrogenic process. Interestingly, no differences in fibrosis were found in the female offspring, suggesting that the adaptation was perpetuated solely by males.

Conclusion: This transgenerational study provides evidence for epigenetic transmission of adaptation to liver fibrosis down the male lineage. This response was absent in female offspring thus explaining the population levels of liver disease.

North-East Postgraduate Conference - NEPG is the largest annual postgraduate conference in the UK, featuring the latest biomedical science research carried out by top postgraduates researchers in the North-East.*