Elucidating the Role of Hypoxia Signaling in Placental Trophoblast Differentiation
Abstract
Preeclampsia is a common and serious complication of pregnancy with no cure except premature delivery. The root cause of preeclampsia is improper development of the placenta, the temporary organ supporting fetal growth. In preeclamptic placentas, a low O2 environment persists due to dysregulated blood flow. My data show that low O2 inhibits differentiation and fusion of progenitor cytotrophoblast cells into a multinucleated syncytiotrophoblast and may thus contribute to the poor placentation in preeclampsia; however, the underlying mechanisms are not well understood. Since low O2 activates a transcription factor complex in cells known as the hypoxia-inducible factor (HIF), I hypothesized that HIF signaling under low O2 impairs placental syncytiotrophoblast formation by altering gene expression. I showed that knockdown of ARNT (a key component of HIF) restores syncytialization under low O2. I also identified downstream targets of HIF that may control this process, which could aid in developing novel therapeutics for preeclampsia.