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评估子宫内膜异位症和不孕女性在位子宫内膜中 TET1 基因表达、DNA 甲基化及其启动子区 H3K27me3 水平。

Assessment of TET1 gene expression, DNA methylation and H3K27me3 level of its promoter region in eutopic endometrium of women with endometriosis and infertility.

机构信息

Department of Reproduction, Poznan University of Medical Sciences, 60-535, Poland.

Department of Histology and Embriology, Poznan University of Medical Sciences, 60-781, Poland.

出版信息

Biomed Pharmacother. 2022 Jun;150:112989. doi: 10.1016/j.biopha.2022.112989. Epub 2022 Apr 27.

DOI:10.1016/j.biopha.2022.112989
PMID:35489280
Abstract

Endometriosis is the cause of infertility. The eutopic endometrium of women with endometriosis showed an aberrant expression pattern of multitude genes. The role of TET1 protein in the pathogenesis of endometriosis and related infertility is not sufficiently known. Further, knowledge on TET1 transcriptional control still remains incomplete. The aim of the study was assessment of TET1 gene expression, DNA methylation and H3K27me3 level of its promoter region in eutopic endometrium of women with endometriosis and infertility. The study included 44 infertile patients with endometriosis (IWE) and 77 infertile (IW) and fertile (FW) patients without endometriosis. The research material was eutopic endometrium. The TET1 mRNA level was analyzed by qPCR. Western blot was used to evaluate the level of TET1 protein. The level of DNA methylation and H3K27me3 level of TET1 gene's promoter region were assessed using HRM and ChIP qPCR, respectively. The level of TET1 expression (TET1 mRNA; TET1 protein level) was lower in IWE during the implantation window (p < 0.001; p = 0.0329). The level of TET1 DNA methylation was higher in the secretory endometrium in mild and advanced IWE (p < 0.004; p < 0.008). H3K27me3 level did not differ between the study groups. The diminished expression of TET1 gene during the secretory phase, may account for the aberrant process of embryonic implantation in infertile endometriosis patients. DNA hypermethylation of TET1 gene is a potential relevant regulator of its expression. H3K27me3 occupancy does not affect the expression of TET1 gene in our study group.

摘要

子宫内膜异位症是导致不孕的原因。患有子宫内膜异位症的女性的在位子宫内膜表现出多种基因的异常表达模式。TET1 蛋白在子宫内膜异位症发病机制及相关不孕中的作用尚不清楚。此外,TET1 转录调控的知识仍然不完整。本研究旨在评估子宫内膜异位症和不孕女性在位子宫内膜中 TET1 基因的表达、DNA 甲基化和启动子区 H3K27me3 水平。该研究纳入了 44 名子宫内膜异位症不孕患者(IWE)和 77 名不孕(IW)和有生育能力(FW)的无子宫内膜异位症患者。研究材料为在位子宫内膜。通过 qPCR 分析 TET1 mRNA 水平。Western blot 用于评估 TET1 蛋白水平。采用 HRM 和 ChIP qPCR 分别评估 TET1 基因启动子区的 DNA 甲基化和 H3K27me3 水平。在着床窗口期间,IWE 中 TET1 表达(TET1 mRNA;TET1 蛋白水平)较低(p<0.001;p=0.0329)。在轻度和晚期 IWE 的分泌期,TET1 DNA 甲基化水平较高(p<0.004;p<0.008)。研究组之间 H3K27me3 水平没有差异。TET1 基因在分泌期的表达减少,可能导致不孕子宫内膜异位症患者胚胎着床过程异常。TET1 基因的 DNA 高甲基化是其表达的潜在相关调节因子。在本研究组中,H3K27me3 占据不影响 TET1 基因的表达。

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