Grant: Operating Grant

The primary role of the placenta is to promote exchange of nutrients and gasses between the mother and the developing baby and it is absolutely essential for a successful pregnancy. Abnormalities in the structure of the placenta are associated with complications during pregnancy that can include miscarriage, intrauterine growth restriction and preeclampsia. Evidence in humans as well as in animal models suggests that babies born from these pregnancies are at an increased risk of hypertension, cardiovascular diseases and diabetes later in life. To date, research has focused on understanding how the changes in placental development can result in these complications. However abnormal placental structure may also result from injury or environmental challenges later in gestation, for example by changes in blood flow (hypoxia). Many studies have characterized adaptive responses in placental physiology, including changes in nutrient transport, in response to these types of challenges. Other studies have characterized changes in placental architecture as adaptive responses. Interestingly, the cell biology and/or molecular mechanisms underlying these adaptations have been largely uncharacterized. Therefore, the overall objective of this proposal is to define the ability of the placenta to adapt to stress during pregnancy as well as to characterize the mechanism(s) by which this occurs. Building on my previous studies investigating the role of trophoblast stem cells in support of mouse placental development, I will address the following hypothesis: The placenta can adapt to challenges during pregnancy through the recruitment and differentiation of trophoblast progenitor cells. The results of these studies will provide novel and important insight into how the placenta maintains its function during pregnancy in order to support the growing fetus. In addition, I expect that they will also lead to a better understanding of the development of complications of pregnancy.