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比较反复种植失败患者和健康生育力妇女的子宫内膜基质细胞中孕激素受体的表达和磷酸化评估。

Evaluation of Expression and Phosphorylation of Progesterone Receptor in Endometrial Stromal Cells of Patients with Recurrent Implantation Failure Compared to Healthy Fertile Women.

机构信息

Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Preventative Gynecology Research Center (PGRC), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Reprod Sci. 2021 May;28(5):1457-1465. doi: 10.1007/s43032-020-00428-8. Epub 2021 Jan 15.

DOI:10.1007/s43032-020-00428-8
PMID:33449351
Abstract

Recurrent implantation failure (RIF) is the repeated failure of good-quality embryos in implantation process following several assisted reproduction cycles. Disruption of the endometrial receptivity is one of the main causes of RIF. Progesterone plays a pivotal role in the endometrial receptivity through the regulation of gene expression pattern by binding to its receptors in the endometrial cells. The aim of this study was to evaluate the expression level of progesterone receptor (PR) and its phosphorylated form in the endometrial stromal cells (eSC) of RIF patients and compare it to the eSC of healthy fertile women as control group. After isolation of the eSC from biopsy samples of RIF patients and healthy fertile women and their characterization, expression levels of PR mRNA, PR protein, and phospho-Ser294 PR protein were evaluated by quantitative real-time PCR and immunofluorescence staining, respectively. The results demonstrated a significant reduction in PR mRNA expression (P < 0.01.) and phospho-Ser294 PR protein (P < 0.05) level in RIF patients compared to the control group. These data for the first time suggest that the expression of PR and its phosphorylated form are impaired in RIF patients. Therefore, designing therapeutic methods for improving PR expression status and its regulation in the endometrium of RIF patients may help in improving the final reproductive outcomes of these cases.

摘要

反复着床失败(RIF)是指在多次辅助生殖周期后,优质胚胎在着床过程中反复着床失败。子宫内膜容受性的破坏是 RIF 的主要原因之一。孕激素通过与子宫内膜细胞中的受体结合,调节基因表达模式,在子宫内膜容受性中发挥关键作用。本研究旨在评估 RIF 患者和健康生育女性的子宫内膜基质细胞(eSC)中孕激素受体(PR)及其磷酸化形式的表达水平,并将其与对照组进行比较。从 RIF 患者和健康生育女性的活检样本中分离出 eSC 并对其进行特征描述后,通过实时定量 PCR 和免疫荧光染色分别评估 PR mRNA、PR 蛋白和磷酸化 Ser294 PR 蛋白的表达水平。结果表明,与对照组相比,RIF 患者的 PR mRNA 表达(P<0.01)和磷酸化 Ser294 PR 蛋白水平(P<0.05)显著降低。这些数据首次表明,PR 及其磷酸化形式的表达在 RIF 患者中受损。因此,设计改善 RIF 患者子宫内膜中 PR 表达状态及其调节的治疗方法可能有助于改善这些病例的最终生殖结局。

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