Project 461838

Successful pregnancy depends on the coordinated development of the placenta and uterine tissues. To function properly, the placenta must grow into the wall of the uterus in a precisely regulated manner. If this process (called placental invasion) is insufficient, the fetus might be miscarried, or the baby born preterm and/or too small. Preeclampsia is the most common pregnancy complication that arises from insufficient placental invasion and it can have severe health consequences for both mother and baby. The overall goal of these studies is to clarify the roles of bone morphogenetic protein 2 (BMP2) in human placental development. We have already shown that this growth factor (BMP2) is present in the placenta and uterus, and that its levels are low in placentas from women with preeclampsia. We have demonstrated that BMP2 enhances the invasive behaviour of human placental trophoblast cells. We also know that BMP2 can enhance changes in cells of the uterus that are important for embryo implantation and placental development (i.e. decidualization). Our proposed studies will use established human cell models to define how BMP2 regulates uterine cell function. In addition, we will use exciting new 3D placental trophoblast cell models to study how BMP2 regulates invasive trophoblast differentiation. These studies will help us learn more about placental development and might lead to clinical advancements in the treatment of common pregnancy complications such as preeclampsia, pregnancy loss, and preterm labor.