N-glycosylation of uterine endometrium determines its receptivity

Abstract

Glycosylation alters the molecular and functional features of glycoproteins, which is closely related with many physiological processes and diseases. During "window of implantation", uterine endometrium transforms into a receptive status to accept the embryo, thereby establishing successful embryo implantation. In this article, we aimed at investigating the role of N-glycosylation, a major modification type of glycoproteins, in the process of endometrial receptivity establishment. Results found that human uterine endometrial tissues at mid-secretory phase exhibited Lectin PHA-E+L (recognizes the branched N-glycans) positive N-glycans as measured by the Lectin fluorescent staining analysis. By utilizing in vitro implantation model, we found that de-N-glycosylation of human endometrial Ishikawa and RL95-2 cells by tunicamycin (inhibitor of N-glycosylation) and peptide-N-glycosidase F (PNGase F) impaired their receptive ability to human trophoblastic JAR cells. Meanwhile, N-glycosylation of integrin αvβ3 and leukemia inhibitory factor receptor (LIFR) are found to play key roles in regulating the ECM-dependent FAK/Paxillin and LIF-induced STAT3 signaling pathways, respectively, thus affecting the receptive potentials of endometrial cells. Furthermore, in vivo experiments and primary mouse endometrial cells-embryos coculture model further verified that N-glycosylation of mouse endometrial cells contributed to the successful implantation. Our results provide new evidence to show that N-glycosylation of uterine endometrium is essential for maintaining the receptive functions, which gives a better understanding of the glycobiology of implantation.

Keywords: N-glycosylation, LIFR; avβ3; embryo implantation; endometrial receptivity.