Dr Williamson - PIP-C Study
Investigation of the effect of male cholestasis on the epigenome of sperm and the impact on the health of children of men with cholestasis
Awarded to King's College London
Professor Catherine Williamson, Women’s Health, King’s College London
The total grant awarded is £25,000
Duration of award: 17 June 2016 to 31 August 2023 (extended due to COVID)
Award details: Investigation of the effect of male cholestasis on the epigenome of sperm and the impact on the health of children of men with cholestasis.
Summary
The principal aim of this study is to investigate whether cholestatic conditions like PSC in men of reproductive age can alter the characteristics of their sperm and have an impact on the health of their children. For some years we have known that the health of fathers at the time of conception has an influence on the health of their children. Studies looking at the effect of paternal obesity and other metabolic disorders, such as diabetes, have found that the children of these men have an increased risk of obesity and diabetes. More recently, researchers have been able to identify changes in the structure and function of sperm of men with metabolic disorders (described as epigenetic alterations). Further studies have been able to show that changes to the structure of sperm can result in changes to the development of the fetus, and can influence its lifelong health.
To study whether paternal PSC could increase the risk of metabolic disorders in children, we have been approaching men with PSC to ask if they will donate a sample of sperm so we can study whether this has epigenetic changes that may be of relevance to their children’s health. We are comparing these sperm samples with those given by men who do not have PSC. As many men with PSC also have inflammatory bowel disease, we are also comparing changes in the sperm of men with PSC plus inflammatory bowel disease to those with PSC and no inflammatory bowel disease.
Sadly this study has been delayed by (1) the COVID-19 pandemic and (2) problems re-starting research studies after the pandemic. The study is now re-starting and we hope to complete recruitment within 12 months.
Professor Catherine Williamson
“This grant from PSC Support has enabled my team to develop new collaborations with specialists that manage men with PSC. We are studying whether PSC causes changes in the sperm of affected men that might influence the health of their children, and whether co-existing inflammatory bowel disease increases the impact on child health. We are so grateful to PSC Support for giving us this funding and for being patient while the study suffered considerable delays during the COVID-19 pandemic. If we show changes in the sperm of men with PSC we have some evidence that the drug UDCA may reverse the impact of these changes on children. Future work will study the impact of UDCA in more detail.“ Professor Catherine Williamson (April 2023)
