Proteomic studies of human placentas reveal partnerships associated with preeclampsia, diabetes, gravidity, and labor

Abstract

AbstractVEGFR2 is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX and PICALM. The oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), the tissue-resident macrophages. MDMX, PICALM, and V1aR were on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20-150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood-brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before labor. We found select associations between higher MDMX, PICALM, OT-R and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations between PICALM-OT-R (p<2.7x10-8), PICALM-V1aR (p<0.006), and OT-R-V1aR (p<0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX.