poFUT1 promotes uterine angiogenesis and vascular remodeling via enhancing the O-fucosylation on uPA

Uterine angiogenesis and vascular remodeling play critical roles in determing the normal menstrual cycle and successful pregnancy. Poor uterine angiogenesis usually results in pregnancy failure. Protein O-fucosyltransferase 1 (poFUT1) is the key enzyme responsible for O-fucosylated glycan biosynthesis on glycoproteins. However, the dynamic expression and regulation of poFUT1 on the uterine angiogenesis and vascular remodeling remain unknown. Here, we showed that the enlargement of the vascular lumen in the secretory phase was greater than that in the proliferative phase of the uterine endometrium during menstrual cycle; whereas there was a narrower vessel lumen and fewer blood vessels in the decidua from miscarriage patients than in that from healthy pregnancy women. Additionally, the expression of poFUT1 was increased in the uterine endometrium during the secretory phase compared with that in the proliferation phase, and its expression was decreased in the uterus of miscarriage patients compared with that of the healthy pregnancy women. Using hESCs and a mouse model, we demonstrated that poFUT1 increased the O-fucosylation on uPA, and activated of the RhoA signaling pathway, thus facilitating uterine angiogenesis and vascular remodeling. We also provide evidence that poFUT1 promotes hESCs angiogenesis by the decreased stemness of hESCs. These findings reveal a new insight into the uterine angiogenesis and vascular remodeling. The study suggests that poFUT1 could be seen as a novel potential diagnostic and therapeutic target for miscarriage.