Endothelial cell-driven migratory remodeling transforms the human endometrial vasculature to establish maternal-fetal circulation in pregnancy

The transformation of the endometrium into the decidua is essential for pregnancy establishment. Maternal endometrial vasculature must undergo remodelling in preparation for maternal-fetal circulation initiation at ~10 weeks gestation. Improper remodeling is associated with increased risk of spontaneous miscarriage and preeclampsia; however, characterization of these adaptations is limited. Using 3D imaging we characterize the vascular morphology from the proliferative phase of the menstrual cycle to the end of the first trimester. We show that the endometrial vasculature is a highly proliferative vascular plexus that expands and transforms into a hierarchical vascular network by ~10 weeks gestation, though this transformation occurs without significant endothelial cell (EC) proliferation post-implantation. Single cell RNA-sequencing analyses reveal a pro-migratory decidual EC signature and identify novel pathways that may contribute to the development of maternal-fetal circulation. Thus, disruption of EC-driven migratory remodeling could limit network efficiency and contribute to the development of pregnancy pathologies.