O‑GlcNAc modification influences endometrial receptivity by promoting endometrial cell proliferation, migration and invasion

O-GlcNAc 修饰通过促进子宫内膜细胞增殖、迁移和侵袭来影响子宫内膜容受性

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作者:Xiao Han, Xiaoxue Li, Huan Liu, Hongshuo Zhang, Aoying Li, Ming Dong, Yuefei Xu, Bin Yan, Linlin Sui, Ying Kong

Abstract

O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling. This dynamic modification is dependent on the ambient glucose concentration and is catalyzed and removed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively. The present study aimed to determine the role of O‑GlcNAcylation during embryo implantation by inhibiting or enhancing its function and expression. The results revealed that the expression of O‑GlcNAc‑modified proteins in the human secretory endometrium was higher than that of the endometrium during the proliferative phase, as determined via western blotting and immunohistochemistry. Additionally, the level of endometrial O‑GlcNAc modification increased gradually from the pre‑receptive to the receptive phase, which was then decreased during the non‑receptive phase. In endometrial cells, RNA interference was utilized to reduce the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification. The results revealed that increasing the level of O‑GlcNAc modification enhanced cellular proliferation, migration, invasion and adhesion, thereby promoting embryo implantation. It is hypothesized that O‑GlcNAc modification serves an important role in the regulation of endometrial receptivity and embryo implantation. The results of the present study may have important implications for the understanding of female fertility and may help improve infertility treatments.

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