New research led by Professor Catherine Williamson, School of Life Course Sciences, shows that using drugs to treat male mice with cholestasis reduced the likelihood of male offspring developing high blood pressure.
It is known that the 16 year old children of mothers with the liver disease cholestasis have higher blood cholesterol and are more likely to be overweight. In a study published in the International Journal of Obesity, Professor Williamson and her colleagues hypothesised therefore that the offspring of fathers with cholestasis may also be susceptible to similar metabolic diseases.
The most common chronic cholestatic liver diseases affecting men are primary sclerosing cholangitis (PSC) and primary biliary cholangitis occurring in as many as 16 in 100,00 and 40 in 100,000 of the general population respectively: as many as 27,500 people in the UK. The bile ducts of patients with these diseases become narrowed from inflammation and fibrosis and, over time, can block completely. This interrupts the flow of bile from the liver and causes a variety of symptoms in some cases ultimately lead to biliary cirrhosis, portal hypertension and liver failure.
Initial research focussed on mouse models, inducing cholestasis with a diet supplemented with bile acid for 10 weeks prior to mating. Male offspring when fed a high-fat diet at 12 weeks old developed higher cholesterol and higher blood pressure than the offspring of 'healthy' males. The authors also wanted to know if clinical intervention, using a drug commonly used to treat cholestasis, could prevent metabolic disease occurring in future generations. Treatment of fathers with the drug ursodeoxycholic acid (UDCA) before conception reduced the blood pressure of subsequent offspring to normal levels.
In a major step towards understanding the life course of health, these results show that the health of a father directly affects the health of his children. These findings could have significant impact on the families of men suffering from cholestasis and so the charity PSC Support has funded the team to take this work forward in men with the disease.
Speaking of the study Professor Williamson said:
'The findings in mice have been very helpful to enable us to understand the impact of cholestasis upon offspring health. It is now essential to see if the same phenomenon occurs in humans. If we have the same findings when we study men with PSC, we hope that the results will enable doctors to consider UDCA treatment in men with cholestasis, not just to improve a father's disease, but also to maximise the health of his children'