Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian 116044, China.
Department of Pathology, the Secondary Affiliated Hospital of Dalian Medical University, Dalian 116000, China.
Biol Reprod. 2023 Apr 11;108(4):553-563. doi: 10.1093/biolre/ioad011.
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.
滋养层细胞在妊娠早期的胎盘血管生成中起着至关重要的作用。滋养层功能障碍导致血管重塑缺陷和血管生成受损，这被认为是胎盘功能不全和妊娠失败的主要原因。蛋白 O-岩藻糖基转移酶 1（poFUT1）主要负责糖蛋白上 O-岩藻糖基化聚糖的生物合成，poFUT1 缺陷导致小鼠胚胎致死。然而，poFUT1 在滋养层介导的人胎盘血管形成中的表达和功能仍不清楚。在本研究中，我们发现流产患者的绒毛和蜕膜中的血管比正常妊娠妇女少。与正常妊娠妇女相比，流产患者的滋养层细胞中 poFUT1 的表达减少。通过 HTR/SVneo 细胞和体内绒毛尿囊膜分析，我们证明了 poFUT1 促进了滋养层细胞的增殖、迁移能力和血管生成潜力。结果还表明，poFUT1 上调了 uPA 上的 O-岩藻糖基化，促进了 uPA 和 uPAR 的结合，激活了 RhoA 信号通路，进一步增强了滋养层细胞的血管生成能力。本研究为 poFUT1/O-岩藻糖基化与胎盘血管生成之间的关系提供了新的证据。这些发现可能为流产患者提供潜在的诊断生物标志物和靶向治疗方法。
