Nelson Lab:

  The long-term goal of our studies is to determine how the human placenta contributes to normal and abnormal pregnancy development. The trophoblast layer of human placental villi interfaces the mother and fetus, transporting nutrients to the baby and secreting multiple protein and steroid products that are important for the maintenance of pregnancy. Differentiation of the trophoblast layer is a tightly regulated process that proceeds on a continuum from a proliferative, undifferentiated, mononucleated cytotrophoblast to a terminally differentiated syncytiotrophoblast. Under-perfusion, villous hypoxia, and enhanced fibrin deposition are characteristic of placentas from pregnancies complicated by fetal growth restriction and preeclampsia. Our NIH-supported lab studies the molecular and cellular mechanisms that regulate normal trophoblast differentiation and the altered differentiation and enhanced apoptosis that occurs in response to hypoxia. We use primary cultures of human trophoblast to investigate the roles of peroxisome proliferator activated receptor-gamma (PPAR-g) and prostaglandins to mediate the effects of exogenous stimuli, including hypoxia, homocysteine, and fibrin matrix, on trophoblast biology. We dissect signaling pathways involving the Bcl-2 proteins and caspases in our studies of apoptosis. We also study the steps in apoptosis that are unique in the syncytiotrophoblast and that contrast this syncytium with a cell containing only one nucleus, the cytotrophoblast. Findings in vitro are then examined in placentas of women with pregnancy pathologies to determine if the mechanisms involved with differentiation and apoptosis in vitro apply to the in vivo state.

Muglia Laboratory