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O-连接的 N-乙酰氨基葡萄糖修饰通过促进子宫内膜细胞的增殖、迁移和侵袭来影响子宫内膜的容受性。

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

机构信息

Core Laboratory Glycobiol and Glycogen, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.

Clinical Medicine of 2016, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.

出版信息

Oncol Rep. 2019 Nov;42(5):2065-2074. doi: 10.3892/or.2019.7317. Epub 2019 Sep 16.

DOI:10.3892/or.2019.7317
PMID:31545463
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.

摘要

O-连接β-N-乙酰葡萄糖胺(O-GlcNAc)修饰是一种动态的翻译后修饰过程,涉及许多关键的生物过程,包括细胞周期调控、营养代谢和细胞外信号转导。这种动态修饰依赖于环境葡萄糖浓度,并分别由 O-GlcNAc 转移酶(OGT)和 O-GlcNAcase(OGA)催化和去除。本研究旨在通过抑制或增强其功能和表达来确定 O-GlcNAc 化在胚胎植入过程中的作用。结果表明,通过 Western blot 和免疫组织化学法检测,人分泌期子宫内膜中 O-GlcNAc 修饰蛋白的表达高于增生期子宫内膜。此外,子宫内膜 O-GlcNAc 修饰水平从预接受期逐渐增加到接受期,然后在非接受期下降。在子宫内膜细胞中,利用 RNA 干扰技术降低两个关键的 O-GlcNAc 合成和分解酶,即 OGT 和 OGA 的表达,以间接增加或减少 O-GlcNAc 修饰水平。结果表明,增加 O-GlcNAc 修饰水平可增强细胞增殖、迁移、侵袭和黏附,从而促进胚胎植入。研究假设 O-GlcNAc 修饰在调节子宫内膜容受性和胚胎植入中发挥重要作用。本研究的结果可能对理解女性生育能力具有重要意义,并有助于改善不孕治疗。

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The Sweet Relationship between the Endometrium and Protein Glycosylation.子宫内膜与蛋白质糖基化的甜蜜关系。
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