PoFUT1 Promotes Placental Angiogenesis by Increasing O-Fucosylation of uPA in Trophoblast Cells

Abstract

Background: Trophoblast cells are responsible for placenta angiogenesis and vascular remodeling in the first-trimester pregnant. An early disruption of trophoblast function leads to vascular dysfunction and impaired angiogenesis, which usually results in pregnancy failure or placental insufficiency underlying pregnancy complications. Protein O-fucosyltransferase 1 (poFUT1) is responsible for O-fucosylated glycans on glycoproteins. However, the expression character of poFUT1 in early pregnancy and miscarriage, and the regulation of poFUT1 on angiogenesis and vessels remodeling remain unclear. Methods: We detected the lumen and blood vessels in the embryonic villi and endometrium decidual from normal pregnancy women and miscarriage women. Employing HTR/SVneo and in vivo chorioallantoic membrane (CAM) assay, we investigated the underlying mechanisms of poFUT1 in trophoblast angiogenesis. Findings: we found that the narrower of the lumen and fewer blood vessels were observed in villi and decidial from miscarriage patients than normal pregnancy women. The expression of poFUT1 also decreased in villi trophoblast and extravillous trophoblast (EVT) from miscarriage patients compared with normal pregnancy women. Employing HTR/SVneo and in vivo chorioallantoic membrane (CAM) assay, we confirmed poFUT1 promote the proliferation, migration ability and angiogenesis potential of trophoblast cells. The results also revealed that poFUT1 upregulated O-fucosylation on uPA, activated RhoA signaling pathway, further enhanced angiogenic capacity of trophoblast cells. Interpretation: Our study provides new evidence for a relationship between poFUT1 and angiogenesis and uterine vessels remodeling. These finding may help develop diagnostic biomarkers and targeted therapies for miscarriage patients. Funding: National Natural Science Foundation of China. Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: This study was approved by the Clinical Ethics Review Board of Dalian Medical University.