Congratulations to CTR members Professor Dino Giussani and Professor Sue Ozanne who have, with Professor Mike Murphy (MRC Mitochrondrial Biology Unit), been awarded a £1.3m grant from the Medical Research Council (MRC) to study the relationship between obesity in pregnancy and cardiovascular effects in the offspring. Their project 'Maternal Obesity: Translatable Programmed Cardiovascular Dysfunction in Offspring' will run for three years between 2021 and 2024.
Obesity has reached epidemic proportions, affecting more than 1.4 billion adults worldwide. The concern about obesity catapults to a much greater level of importance and significance when considering maternal obesity. In a 2019 report as Chief Medical Officer, Dame Sally Davies highlighted that over half of women in the UK are now obese or overweight during pregnancy. This is of the gravest concern as obesity during pregnancy not only has immediate detrimental effects on the mother, but also on her children, thereby propagating adverse health risks onto the next generation. Robust and rapidly accumulating evidence derived from human studies as well as from experimental animal models shows that maternal obesity can markedly increase the risk of cardiovascular disease in the offspring, even when the progeny feed on a healthy diet and in the absence of them becoming obese. This highlights that it is something about exposure of the embryo or fetus to an obesogenic environment during gestation itself that either triggers a fetal origin of cardiovascular dysfunction and/or increases the risk of heart disease in the adult offspring. However, the mechanisms linking obesogenic pregnancy and an increased cardiovascular risk in the offspring remain unclear, preventing the identification of targets for intervention.
This project exploits novel technology in an ovine model of obesogenic pregnancy to test the hypothesis that maternal obesity promotes a fetal origin of cardiovascular disease via adverse mechanisms triggered by mitochondria-derived oxidative stress. Causality will be addressed using mitochondria-targeted antioxidant intervention. The proposed study design adopts an integrative approach combining experiments of in vivo cardiovascular function with those at the isolated organ, cellular and molecular levels in fetal and adult offspring of both sexes. In addition, the project offers excellent training in highly vulnerable skills in fetal cardiovascular surgery and in the direct in vivo investigation of maternal, fetal and adult offspring cardiovascular function using state-of-the-art technology in a world-class environment for research that will help shape the next generation of biomedical research leaders.