a1,3-fucosylation of MEST promotes embryo implantation by activating translation initiation

Abstract Embryonic trophoblast implanting into the uterus is the gateway for successful pregnancy. Dysfunctions of trophoblast cause pregnancy failure. Protein glycosylation plays crucial roles in reproduction process. However, it remains unclear if the glycosylation of trophoblasts involves in embryo implantation. By glycomics, proteomics combined with translatomics, our results revealed the that decreased α1,3-fucosylation, especially difucosylated Lewis Y (LeY) glycan, in the villus trophoblast of miscarriage patients compared with normal pregnancy women. Downregulating LeY by silencing key enzyme fucosyltransferase IV (FUT4) inhibited trophoblast implantation potential. Using proteomics analysis, we identified MEST scaffolding LeY at Asn163, and its expression was enhanced trophoblast implantation. We also provided novel evidence showing that decreased LeY modification on MEST dramatically hampered it binding with translation factor eIF4E2, and inhibited implantation-related gene translation initiation, which caused embryo implantation failure. The α1,3-fucosylation of MEST by FUT4 may serves as a new biomarker for evaluating the functional state of pregnancy and target for infertility treatment.