poFUT1 Promotes Endometrial Decidualization by Enhancing the O-Fucosylation of Notch1

Uterine stromal cell decidualization is critical for embryo implantation. Dysfunctional decidualization leads to implantation failure or miscarriage and even initiates pregnancy associated disorders in subsequent pregnancy trimesters. Protein glycosylation is involved in many physiological and pathological processes. Protein O-fucosyltransferase 1 is the key enzyme for the O-fucosylation of proteins. However, the role and mechanism of poFUT1 in hESC decidualization remain elusive. In the current study, we reported that the level of poFUT1 increased in stromal cells in the secretary phase relative to those in the proliferative phase of the menstrual cycle and decreased in the stromal cells of miscarriage patients relative to women with healthy early pregnancies. Using hESC lines and a mouse model, we found that poFUT1 promoted hESC decidualization. We also demonstrated that poFUT1 increased O-fucosylation on Notch1 in hESC, which further activated the Notch1 signalling pathway. Activated Notch1 (NICD) is a specific transfactor of the PRL and IGFBP1 promoters and may increase PRL and IGFBP1 transcriptional activity, further inducing hESC decidualization. Taken together, our findings provide a new mechanistic perspective on poFUT1 in uterine decidualization that may be a useful diagnostic and therapeutic target for miscarriage. Funding Statement: This work was supported by the National Natural Science Foundation of China (No: 31670810 and 31770857). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the Clinical Ethics Review Board of Dalian Medical University.