Professor Lucilla Poston

1. Pre-eclampsia.

Pre-eclampsia remains a common disorder of pregnancy, affecting 3-5% of all pregnancies and threatening the health, and indeed the lives of the mother and baby. Our group has a long standing interest in maternal endothelial function  in pre-eclampsia and the role of oxidative stress the aetiology of the disease. Early research from our group was amongst the first to show clear evidence for endothelial dysfunction in women with pre-eclampsia, now considered to play a pivotal role in  the maternal syndrome. We have actively pursued the hypothesis that oxidative stress, arising from placental dysfunction, and through exaggeration of the inflammatory response and endothelial dysfunction, is intimately involved in the origins of the disease.

In 1999, in a small study, we showed that antioxidants improved vascular function in women at risk of the disease, and the study showed early promise as fewer women developed pre-eclampsia. However a subsequent nationwide randomised controlled trial conducted by our unit showed no benefit of prophylactic treatment with vitamins C and E.  In common with other cardiovascular diseases associated with oxidative stress it appears that antioxidants will not be able to provide an easy preventative strategy, but this does not mitigate against a role for oxidative stress, and we actively pursue research in that area. Having worked for some time in development of predictive tests for pre-eclampsia, and published patents in that area, we have recently joined the international study ‘SCOPE’  which aims to develop accurate predictive tests for pre-eclampsia, pre-term labour and fetal growth restriction. SCOPE draws upon scientific and clinical expertise from Universities across the world, and provides a unique opportunity for not only elaborating predictive tests but also through state-of-the art proteomics and bioinformatics, providing new insights into the aetiology of the three most common disorders affecting pregnant women.  

Research in the unit run by Professor Andrew Shennan, is involved in a very practical problem, the accurate measurement of blood pressure in pregnant women. The last few years has seen the development of a wide range of automated instruments designed to measure blood pressure, and intended to provide replacements for the mercury sphygomanometer. Unfortunately, many have not been validated, especially for use in pregnancy. Professor Shennan’s team are accredited to validate new blood pressure measuring devices and have recently developed new devices for accurate measurement of blood pressure in the clinic, and a new, robust and inexpensive device for use in the developing world.

2. Developmental Programming of Adult Disease.

The scientific community is increasingly aware that susceptibility to disease may originate in the earliest stages of human life. Population studies world-wide have shown that individuals who are undernourished in utero are more susceptible to cardiovascular and metabolic disease in later life.

Research from Professor David Barker’s unit at Southampton University over the last 20 years has sparked a remarkable resurgence in interest into the physiology of fetal nutrition. Working in collaboration with the Southampton Unit and colleagues at Cambridge and Nottingham universities, our Unit has developed several rodent models to probe the mechanisms underlylng the developmental origins of adulthood disease. Our focus has not been on undernutrition, but on overnutrition as we have shown that a maternal diet rich in fat and calories can also lead to development of disease in the offspring. We have shown that rats and mice exposed in utero to a diet rich in fat and simple sugars develop hypertension, insulin resistance and obesity. 

The observation that maternal obesity and a hypercalorific diet in rodents can ‘programme’ obesity in the developing child has generated considerable interest, not to mention concern, should it be proven that this also occurs in human pregnancy. Indeed, some observational studies from other groups working with women and their children have provided some evidence to support a similar transmission of an obesogenic trait from mother to baby.

We are now pursuing our animal models with a view to understanding the underlying mechanisms, with particular focus on the hypothesis that the maternal nutritional environment may permanently ‘rewire’ the appetite control centres of the developing hypothalamus. Unravelling the epigenetic mechanisms which ensure persistent alteration of physiological and biochemical function from the in utero and early post natal environment, through to adult life presents a terrific challenge Some insight has  been gained from recent work in our group directed by Dr Josie McConnell  which has suggested that the mitochondrion may carry the ‘memory’ and be causative in the later development of disease.