Cannabinoid and planar cell polarity signaling converges to direct placentation
Yeon Sun Kim, Yingju Li, Jia Yuan, Jean‐Paul Borg, Xiaofei Sun, Sudhansu K. Dey
Abstract
Significance During placentation, some trophoblast cells, termed spiral artery trophoblast giant cells (SpA-TGCs), invade the maternal decidua and replace arterial endothelial cells to increase blood supply to the placenta; how this directional trophoblast migration occurs remains unknown. We show here that planar cell polarity (PCP) signaling mediated by VANGL2 in SpA-TGCs plays a key role in trophoblast movement and successful placentation. Mice with SpA-TGC progenitors deficient in Vangl2 had pregnancy termination in mid-gestation due to increased random cell protrusion and compromised cell migration. We also found endocannabinoid signaling intersects with PCP signaling in directing trophoblast migration by direct association of CB1 and VANGL2 . These results demonstrated that trophoblast invasion in placentation requires organized PCP.