Grant: Operating Grant: ECI grants in Maternal, Reproductive, Child & Youth Health

Proper placental function is essential for the health of the fetus and mother during pregnancy. Placental dysfunction, which is when cells in the placenta do not form or function properly, is a characteristic of the common pregnancy complications preeclampsia and intrauterine growth restriction. Importantly, these complications significantly affect the lifelong health of mothers and their babies. The cell that forms the surface of the placenta, the syncytiotrophoblast (ST), is particularly important in the development of placental dysfunction. Unfortunately, there are large gaps in our knowledge about basic ways that the ST functions. This hampers our ability to understand how we could correct ST function in placental dysfunction in order to treat both mothers and their babies. Here we will examine how the ST establishes and maintains the separated arrangement of proteins and cellular components between the "top" and "bottom" side of the cell. This is known as cell polarity, and it is important for cellular function to allow for delivery of nutrients and waste between the mother and the fetus. We will examine the role of the Par polarity complex, a group of proteins known to control cell polarity that have not been studied in the placenta. The Par complex also controls the arrangement of the cytoskeleton, endocytosis, and response to inflammation. These are critical processes that maintain ST function and are disrupted in placental dysfunction, but how these processes are carried out in ST are mostly unknown. Therefore, these studies will increase our knowledge about fundamental aspects of ST cell biology. The knowledge we gain will help us to understand the unique ways in which the ST functions and in the future will lead to the identification of new therapeutic targets to treat placental dysfunction and improve outcomes for both mothers and their children.