PRMT5 介导的 HOXA10 精氨酸 337 甲基化在子宫内膜上皮细胞接受性中的作用。

IF 2.5 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical and biophysical research communications Pub Date : 2024-11-15 DOI:10.1016/j.bbrc.2024.151004
Zhiwen Cao , Jinwen Jiang , Yiting Wang , Yuhang Lu , Min Wu , Xin Zhen , Xinyu Cai , Haixiang Sun , Guijun Yan
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引用次数: 0

摘要

胚胎能否成功着床在很大程度上取决于子宫内膜上皮的接受能力,这一过程受各种分子机制的调控。由于传统评估方法的局限性,对接受辅助生殖治疗的不孕症患者,尤其是与子宫腺肌症相关的不孕症患者的子宫内膜接受能力进行评估面临巨大挑战。在这项研究中,我们收集了子宫腺肌症相关不孕症患者胚胎移植导管顶端残留的子宫内膜上皮细胞。高通量测序显示,这些细胞中的蛋白精氨酸甲基转移酶 5 (PRMT5) 明显下调。功能测试表明,PRMT5 与子宫内膜接受性和着床的关键转录因子同工酶 A10(HOXA10)相互作用并使其甲基化。PRMT5对HOXA10精氨酸337处的甲基化增强了其稳定性,并促进了对子宫内膜分化和粘附至关重要的基因的转录激活。PRMT5的下调导致HOXA10活性降低,从而导致子宫内膜接受能力受损和随后的种植失败。这些发现阐明了PRMT5下调对HOXA10功能产生负面影响的关键途径,为了解子宫腺肌症相关不孕症中植入失败的分子机制提供了新的视角。这项研究不仅加深了我们对子宫内膜接受性调控机制的理解,而且还发现了增强受影响患者子宫内膜功能的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Role of PRMT5 mediated HOXA10 arginine 337 methylation in endometrial epithelial cell receptivity
A successful embryo implantation relies heavily on the receptivity of the endometrial epithelium, a process regulated by various molecular mechanisms. Evaluating endometrial receptivity in infertility patients undergoing assisted reproductive treatment, particularly those with adenomyosis related infertility, poses significant challenges due to limitations associated with conventional assessment methods. In this study, we collected residual endometrial epithelial cells from the tips of embryo transfer catheters in patients with adenomyosis related infertility. High throughput sequencing revealed a marked downregulation of protein arginine methyltransferase 5 (PRMT5) in these cells. Functional assays demonstrated that PRMT5 interacts with and methylates homeobox A10 (HOXA10), a crucial transcription factor for endometrial receptivity and implantation. The methylation of HOXA10 at arginine 337 by PRMT5 enhances its stability and promotes the transcriptional activation of genes essential for endometrial differentiation and adhesion. The downregulation of PRMT5 led to decreased HOXA10 activity, resulting in impaired endometrial receptivity and subsequent implantation failure. These findings elucidate a critical pathway where PRMT5 downregulation negatively impacts HOXA10 function, providing new insights into the molecular mechanisms underlying implantation failure in adenomyosis related infertility. This study not only advances our understanding of the regulatory mechanisms governing endometrial receptivity but also identifies potential therapeutic targets for enhancing endometrial function in affected patients.
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来源期刊
Biochemical and biophysical research communications
Biochemical and biophysical research communications 生物-生化与分子生物学
CiteScore
6.10
自引率
0.00%
发文量
1400
审稿时长
14 days
期刊介绍: Biochemical and Biophysical Research Communications is the premier international journal devoted to the very rapid dissemination of timely and significant experimental results in diverse fields of biological research. The development of the "Breakthroughs and Views" section brings the minireview format to the journal, and issues often contain collections of special interest manuscripts. BBRC is published weekly (52 issues/year).Research Areas now include: Biochemistry; biophysics; cell biology; developmental biology; immunology ; molecular biology; neurobiology; plant biology and proteomics
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