Grant: Project Grant

Excess body weight is a serious concern for many women of reproductive age. Being overweight or obese has several potential effects on the health of mother and baby, especially because of higher rates of complications like gestational diabetes, high blood pressure and spontaneous pregnancy loss. These effects may be related to an effect of excess body weight on the very earliest developmental events, such as the development of the placenta. The placenta is the essential link between the mother and developing baby, so if it does not form properly, there can be severe consequences. My proposal aims to examine the effects of obesity in altering the cell make-up of the fetal-maternal environment in early human pregnancy. We hypothesize that the state of obesity alters the local makeup and function of maternal and fetal cells leading to impaired placenta function. To achieve these aims, we will directly compare placenta and uterine tissues obtained from obese and non- obese women in the first trimester of pregnancy, and findings from human clinical specimens will be mechanistically examined using an obesity mouse model. I will compare cellular, molecular and genetic characteristics of the two groups by measuring blood chemistry, cellular composition (maternal and fetal), cell function and gene expression. The proposed studies will establish if there are inherent differences in the cell biology of placentas from obese women compared to non-obese women. I anticipate that there will be differences in fetal-maternal cellular composition between these groups of women. These changes in the local placental-uterine environment are predicted to modify placental function, in part by altering gene expression. Results from these experiments will lay the groundwork for future studies aiming to define the role of obesity in the development of pregnancy-related disorders.