Role of poFUT1 and O-fucosylation in placental angiogenesis†

Trophoblast cells are critical to placental angiogenesis in the first trimester of pregnancy. Dysfunction of trophoblast leads to defective vascular remodeling and impaired angiogenesis, which is believed as the major cause of placental insufficiency and pregnancy failure. Protein O-fucosyltransferase 1 (poFUT1) is mainly responsible for O-fucosylated glycan biosynthesis on glycoproteins, and poFUT1 deficiency causes embryonic lethality in mice. However, the expression and function of poFUT1 in trophoblast-mediated human placental vessel formation remain unclear. In the current study, we showed that fewer blood vessels were observed in the villi and decidua of miscarriage patients than in normal pregnancy women. The expression of poFUT1 was decreased in the trophoblast cells of miscarriage patients compared with normal pregnancy women. Employing HTR/SVneo cells and an in vivo chorioallantoic membrane assay, we demonstrated that poFUT1 promoted the proliferation, migration ability, and angiogenesis potential of trophoblast cells. The results also indicated that poFUT1 upregulated O-fucosylation on uPA, facilitated the binding of uPA and uPAR, activated the RhoA signaling pathway, and further enhanced the angiogenic capacity of trophoblast cells. Our study provides new evidence for a relationship between poFUT1/O-fucosylation and placental angiogenesis. These findings may provide potential diagnostic biomarkers and targeted therapies for miscarriage patients.