Placental hormones and pregnancy health in obese mothers
Project ID: PSM00030
Supervisor: Dr. Amanda Sferruzzi-Perri
Obesity during pregnancy affects maternal and infant health both during pregnancy and for long afterwards. It raises the risk of health complications like maternal diabetes during pregnancy, and increases the susceptibility of the mother to develop metabolic syndrome in the years after delivery. It also leads to neonatal and later life health complications in their infants, such that infants are more prone to develop metabolic impairments themselves in later life. Despite this, the mechanisms operating during pregnancy that lead to these poor pregnancy outcomes in obese women, remain unknown. The placenta is the organ that produces hormones responsible for changing the metabolism of the mother to ensure sufficient nutrients are available for fetal growth during pregnancy. However, to date, little is known about the role of placental hormone production in the development of maternal metabolic complications in pregnancies where the mother is obese. This study aims to identify the importance of placental hormone production for maternal metabolism and offspring health in pregnancies where the mother is obese. It will use samples from pregnant mice that are lean or obese (due to a diet high in sugar and fat) and sequencing and histological methods to characterise the effect of obesity on the placental production of hormones with metabolic effects. It will also use metabolic, molecular and biochemical assays to assess the mother’s ability to use glucose and respond to insulin in obese mice with and without a genetic defect in the placenta that disrupts placental hormone production. Offspring of these pregnancies will also similarly be monitored to identify the relevance of placental hormone production in the programming of metabolic disease in children of obese mothers. This project is funded by a MRC New Investigator Research Grant and Lister Institute Research Prize.
Studies that investigate the mechanisms operating during pregnancy that lead to pregnancy complications and subsequent risk of metabolic diseases in obese women and their infants are of translational and industrial relevance. In particular, this proposed research project will identify placental biomarkers that indicate materno-fetal wellbeing in obese pregnant women. It is anticipated that the proposed research will identify critical factors produced by the placenta that are sensitive to maternal nutrition (obesogenic diets) and which govern maternal metabolic health and offspring development in obese women. These novel placental biomarkers could be used to monitor materno-fetal wellbeing and to diagnose and devise therapies for pregnancy complications including gestational diabetes and fetal metabolic abnormalities, with the ultimate goal of improving pregnancy outcome and long-term health in lean and obese women. I therefore envisage interest from pharmaceutical organisations who may devise diagnostic and therapeutic tools for pregnancy complications and metabolic diseases based on the findings of this study. To facilitate this, I am currently in discussions with Rachel Atfield, Cambridge Enterprise and Andrea Walker, Cambridge Academy of Therapeutics who are helping me to establish industrial collaborations.