O-fucosylation of BMP1 promotes endometrial decidualization by activating BMP/Smad signaling pathway.

Endometrial decidualization is critical to successful uterine receptivity and embryo implantation. Dysfunction of decidualization is associated with some pregnancy-related disorders, including miscarriage. Protein glycosylation is involved in many physiological and pathological processes. Protein O-fucosyltransferase 1 (poFUT1) is a key enzyme responsible for O-fucosylation biosynthesis on glycoproteins. Bone morphogenetic protein 1 (BMP1) is an essential glycoprotein in reproduction. However, the role and molecular mechanism of fucosylated BMP1 in endometrial stromal cell decidualization are still unknown. In the current study, we found that BMP1 contained a potential O-fucosylation site. Moreover, poFUT1 and BMP1 levels in the secretory phase were higher than those in the proliferative phase, and the highest level was observed in the human uterine tissues of early pregnancy, while decreased poFUT1 and BMP1 in the decidua of miscarriage patients. Using human endometrial stromal cells (hESCs), we demonstrated that O-fucosylation of BMP1 was elevated after induction decidualization. Moreover, increasing O-fucosylation of BMP1 by poFUT1 promoted BMP1 secretion to the extracellular matrix, and more actively binds to CHRD, releasing BMP4 bound to CHRD, activating BMP/Smad signaling pathway, thereby accelerating the decidualization of human endometrial stromal cells. In summary, these results suggest that BMP1 O-fucosylation modification combined with poFUT1 upregulation can be a new potential diagnostic and therapeutic target in glycobiology for miscarriage.