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Abstract 478: Identifying Signaling Pathways Regulated by Trophoblasts in Placental Vascular Development Using 3D Tissue Models

The placenta is an essential yet transient organ that supports healthy pregnancy and normal fetal development. Placental vascular dysfunction is associated with preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelets), fetal growth restriction, hemorrhaging, preterm birth, and loss of life. Placental vascular dysfunction can also negatively impact long-term maternal and offspring health, increasing risk for cardiovascular disease, coronary artery calcification, and stroke later in life.
 The vasculature of the maternal-fetal interface is uniquely characterized by the presence of trophoblast cells. Multiple trophoblast cell lineages serve essential functions in both the maternal vascular compartment and the feto-placental angioarchitecture. Functional roles for FGF2, VEGF, and angiopoietin signaling pathways in endothelial vasculogenesis and angiogenesis are well supported by a large body of literature, but there is a gap in knowledge of placenta-specific molecular mechanisms that account for the unique interaction of trophoblasts and endothelial cells. I hypothesize that trophoblasts generate angiogenic signals that promote vascular development at the maternal-fetal interface in both an autocrine and paracrine manner.
 Using 3D assays, I evaluated the role of endovascular cytotrophoblast and syncytiotrophoblast cell lines in establishment of a vascular compartment. Trophoblasts harbor intrinsic angiogenic competency evident by their ability to form angiogenic sprouts and generate 3D vascular networks under defined conditions. My current research implements 3D bioassays, bio-engineered vessels, and chemical inhibition to further investigate paracrine angiogenic signaling between trophoblasts and endothelial cells.
 Our work is the first to evaluate autocrine and paracrine angiogenic properties of trophoblasts under physiological 3D conditions that mimic development. When coupled with histological evaluation of human placenta, these systems will allow us to better evaluate and understand molecular mechanisms of placental vascular development and vascular dysfunction.