62 Unraveling the role of placental trophoblast cells in preeclampsia

Abstract

OBJECTIVES/GOALS: Changes associated with placental vasculature contribute to the progression of gestational hypertensive disease preeclampsia. Caudal-type homeobox-2 (CDX2) regulates trophoblast stem cell differentiation. In this study, we investigate the role of placental CDX2 cells in healthy pregnancy and in conditions of preeclampsia. METHODS/STUDY POPULATION: To understand the role of CDX2 cells, here we collected human placenta samples from the prospectively enrolled cohort and also the de-identified cohort (n=84). We studied CDX2 distribution, and function using a lentivirus-based approach. We studied the CDX2 expression and functional differences using transcriptomics and examined the function in invasion and vasculogenesis in the presence and absence of the new target genes we have discovered in our study. RESULTS/ANTICIPATED RESULTS: Analysis of healthy human placenta samples showed that CDX2-expressing cells were present in fetal chorionic regions and are associated with HLA-G and cytokeratin-7 confirming their trophoblast identity. CDX2 cells demonstrated the potential to form a capillary network akin to endothelial cells. Placental samples from healthy (n=6) and preeclampsia (n=8) patients revealed higher levels of CDX2 expression in preeclampsia. Within preeclampsia CDX2 cells, Natriuretic peptide receptor 1 (NPR1), RET oncogene, and Homeobox D10 (HOXD10) were significantly differentially regulated, including a unique long-non-coding anti-sense RNA (KANSL1-AS1) that affected the function of CDX2 and trophoblast cells in invasion and normal vasculogenesis. DISCUSSION/SIGNIFICANCE: In sum, based on these observations, the present study postulates that CDX2 cells present in a healthy human placenta may serve as a prospective cellular reservoir for angiogenesis. Conversely, altered gene programs within CDX2 cells cause aberrant vascular function that could contribute to the progression of preeclampsia.