Grant: Operating Grant

Excess body fat (obesity) in women who are newly pregnant, may negatively affect the health of mother and fetus, and result in greater risk of pregnancy complications like gestational diabetes, high blood pressure and spontaneous miscarriage. The increased risk may be due to obesity-related changes in immune cells that directly affect embryo implantation, and importantly, development of the placenta. As the placenta is the essential link between the mother and fetus, improper placental development can lead to severe health and survival consequences for the developing fetus. My objective is to determine if obesity alters the cellular make-up and function of immune cells in the fetal-maternal environment, and to examine if these changes affect the repertoire and function of a specialized set of fetal-derived placenta cells (called trophoblasts) during placenta development. I predict that excess fat affects placental development by changing immune cells in the uterus, and that changing these cells threatens the survival and function of trophoblasts. I will directly compare placenta and uterine tissues obtained from women who are obese and of normal weight, in the first trimester of pregnancy. I will compare cellular, molecular, and genetic characteristics of the two groups to determine whether they differ from each other, and if so, how. The study I propose here will establish if there are differences in maternal immune cell function and fetal trophoblast biology between women who are obese and of normal weight; I anticipate that there will be differences in both amounts and kinds of fetal and maternal cells between these groups. These changes in the placental-uterine environment are predicted to modify trophoblast function, in part by altering genetic characteristics. My results will lay the groundwork for future studies aiming to define the role of obesity in the origin of disorders that negatively affect the health and survival of pregnant women and fetuses.