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多个转录组子宫内膜途径的失调与反复着床失败和反复早期妊娠丢失有关。

Dysregulation in Multiple Transcriptomic Endometrial Pathways Is Associated with Recurrent Implantation Failure and Recurrent Early Pregnancy Loss.

机构信息

Academic Unit of Reproductive and Developmental Medicine, Department of Oncology and Metabolism, The Medical School, University of Sheffield, Sheffield S10 2HQ, UK.

Faculty of Dentistry, Universiti Teknologi MARA (UiTM), Sungai Buloh 47000, Malaysia.

出版信息

Int J Mol Sci. 2022 Dec 16;23(24):16051. doi: 10.3390/ijms232416051.

DOI:10.3390/ijms232416051
PMID:36555686
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9782216/
Abstract

Overlapping disease aetiologies associated with multiple altered biological processes have been identified that change the endometrial function leading to recurrent implantation failure (RIF) and recurrent early pregnancy loss (REPL). We aimed to provide a detailed insight into the nature of the biological malfunction and related pathways of differentially expressed genes in RIF and REPL. Endometrial biopsies were obtained from 9 women experiencing RIF, REPL and control groups. Affymetrix microarray analysis was performed to measure the gene expression level of the endometrial biopsies. Unsupervised clustering of endometrial samples shows scattered distribution of gene expression between the RIF, REPL and control groups. 2556 and 1174 genes (p value < 0.05, Fold change > 1.2) were significantly altered in the endometria of RIF and REPL patients’ group, respectively compared to the control group. Downregulation in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the differentially expressed genes (DEGs) in RIF and REPL including ribosome and oxidative phosphorylation pathways. Gene Ontology (GO) analysis revealed ribosomes and mitochondria inner membrane as the most significantly downregulated cellular component (CC) affected in RIF and REPL. Determination of the dysregulated genes and related biological pathways in RIF and REPL will be key in understanding their molecular pathology and of major importance in addressing diagnosis, prognosis, and treatment issues

摘要

重叠的疾病病因与多种改变的生物学过程有关,这些过程改变了子宫内膜的功能,导致反复着床失败(RIF)和反复早期妊娠丢失(REPL)。我们旨在深入了解 RIF 和 REPL 中生物学功能障碍的性质以及相关差异表达基因的途径。从 9 名经历 RIF、REPL 和对照组的女性中获取子宫内膜活检。进行 Affymetrix 微阵列分析以测量子宫内膜活检的基因表达水平。子宫内膜样本的无监督聚类显示 RIF、REPL 和对照组之间基因表达的分散分布。与对照组相比,RIF 和 REPL 患者组的子宫内膜中分别有 2556 个和 1174 个基因(p 值<0.05,倍数变化>1.2)发生了显著改变。KEGG 通路中差异表达基因(DEGs)的下调,包括核糖体和氧化磷酸化通路。GO 分析显示,核糖体和线粒体内膜是 RIF 和 REPL 中受影响最显著的下调细胞成分(CC)。确定 RIF 和 REPL 中失调基因及其相关的生物学途径将是理解其分子病理学的关键,对于解决诊断、预后和治疗问题至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9830/9782216/1e774a963236/ijms-23-16051-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9830/9782216/732991052797/ijms-23-16051-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9830/9782216/b97aba4f048e/ijms-23-16051-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9830/9782216/1e774a963236/ijms-23-16051-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9830/9782216/732991052797/ijms-23-16051-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9830/9782216/b97aba4f048e/ijms-23-16051-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9830/9782216/1e774a963236/ijms-23-16051-g004.jpg

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