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死或生:可育女性子宫内膜基质细胞中选定的凋亡和自噬相关蛋白的探索性分析及其在胚胎植入过程中的潜在作用

Dead or Alive: Exploratory Analysis of Selected Apoptosis- and Autophagy-Related Proteins in Human Endometrial Stromal Cells of Fertile Females and Their Potential Role During Embryo Implantation.

作者信息

Scheliga Iwona, Baston-Buest Dunja M, Haramustek Djamila, Knebel Alexandra, Kruessel Jan-Steffen, Bielfeld Alexandra P

机构信息

Department of OB/GYN and REI (UniKiD), Medical Faculty and University Hospital Duesseldorf, Heinrich Heine University Duesseldorf, 40255 Duesseldorf, Germany.

出版信息

Int J Mol Sci. 2024 Dec 28;26(1):175. doi: 10.3390/ijms26010175.

Abstract

To date, very little is known about how apoptosis and autophagy affect human endometrial stromal cells (ESCs), particularly how these processes might determine the depth of implantation in humans. Before investigating how apoptosis and autophagy might modulate the implantation process in an infertile population, it is necessary to clarify how these processes are regulated in healthy individuals. This study examined the protein expression related to apoptosis and autophagy in primary ESCs from fertile women, particularly in the context of decidualization and embryo contact, using Western blot analysis. This study evaluated the protein expression of apoptosis receptors and autophagy markers during the window of implantation. Previous research has shown that a syndecan 1 (Sdc1) knockdown (kd) in endometrial stromal cell lines increased the sensitivity to apoptosis induced by embryonic stimuli. We aimed to determine if this effect is also present in primary cells and if Sdc1 regulates autophagy. The expression of autophagy- and apoptosis-associated proteins in primary ESCs from fertile individuals was investigated in this preliminary study, along with their impact on the process of human embryo implantation. During decidualization and exposure to embryo contact, we observed an upregulation of apoptosis- and autophagy-related proteins in ESCs. Decidualized ESCs exhibited higher levels of apoptosis receptors, indicating increased sensitivity to embryo-induced apoptosis. Additionally, the increase in basal autophagy proteins suggests a significant role in the implantation process. Sdc1 is potentially involved in regulating apoptosis and autophagy, demonstrating its possible role in modulating implantation-related cell activities. These findings suggest a complex interplay between apoptosis and autophagy in regulating human embryo implantation. The changes in the expression of apoptotic and autophagic proteins in ESCs after decidualization and upon contact with the embryo provide new insights into the cellular mechanisms that underlie successful implantation. These results have potential implications for understanding the pathophysiology of implantation disorders and improving assisted reproductive technologies. The first results of this pilot study need to be verified with a larger sample size in the future.

摘要

迄今为止,对于细胞凋亡和自噬如何影响人子宫内膜基质细胞(ESCs),尤其是这些过程如何决定人类着床深度,我们知之甚少。在研究细胞凋亡和自噬如何调节不育人群的着床过程之前,有必要先阐明这些过程在健康个体中是如何被调控的。本研究使用蛋白质免疫印迹分析,检测了来自有生育能力女性的原代子宫内膜基质细胞中与细胞凋亡和自噬相关的蛋白质表达,尤其是在蜕膜化和胚胎接触的背景下。本研究评估了着床窗口期细胞凋亡受体和自噬标志物的蛋白质表达。先前的研究表明,子宫内膜基质细胞系中Syndecan 1(Sdc1)基因敲低(kd)会增加对胚胎刺激诱导的细胞凋亡的敏感性。我们旨在确定这种效应在原代细胞中是否也存在,以及Sdc1是否调节自噬。在这项初步研究中,我们研究了来自有生育能力个体的原代子宫内膜基质细胞中自噬和凋亡相关蛋白的表达,以及它们对人类胚胎着床过程的影响。在蜕膜化和暴露于胚胎接触过程中,我们观察到子宫内膜基质细胞中凋亡和自噬相关蛋白的上调。蜕膜化的子宫内膜基质细胞表现出更高水平的凋亡受体,表明对胚胎诱导的细胞凋亡敏感性增加。此外,基础自噬蛋白的增加表明其在着床过程中起重要作用。Sdc1可能参与调节细胞凋亡和自噬,证明其在调节与着床相关的细胞活动中的可能作用。这些发现表明细胞凋亡和自噬在调节人类胚胎着床过程中存在复杂的相互作用。蜕膜化后及与胚胎接触后,子宫内膜基质细胞中凋亡和自噬蛋白表达的变化为成功着床的细胞机制提供了新的见解。这些结果对于理解着床障碍的病理生理学和改进辅助生殖技术具有潜在意义。这项初步研究的首批结果未来需要用更大的样本量进行验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dd3/11720002/ccd26201b7de/ijms-26-00175-g001.jpg

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