Gynecological and Obstetrics Department, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, 14049-900, SP, Brazil.
Biochemistry and Immunology Department, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, SP, 14049-900, Brazil.
J Reprod Immunol. 2021 Jun;145:103307. doi: 10.1016/j.jri.2021.103307. Epub 2021 Mar 10.
The aim of this study was to identify the key similarities between the eutopic endometrium of women with endometriosis and chlamydia-induced endometritis taking into account tissue microenvironment heterogeneity, transcript gene profile, and enriched pathways. A meta-analysis of whole transcriptome microarrays was performed using publicly available data, including samples containing both glandular and stromal endometrial components. Control samples were obtained from women without any reported pathological condition. Only samples obtained during the proliferative menstrual phase were included. Cellular tissue heterogeneity was predicted using a method that integrates gene set enrichment and deconvolution approaches. The batch effect was estimated by principal variant component analysis and removed using an empirical Bayes method. Differentially expressed genes were identified using an adjusted p-value < 0.05 and fold change = 1.5. The protein-protein interaction network was built using the STRING database and interaction score over 400. The Molecular Signatures Database was used to analyse the functional enrichment analysis. Both conditions showed similarities in cell types in the microenvironment, particularly CD4 and CD8 Tem cells, NKT cells, Th2 cells, basophils, and eosinophils. With regards to the regulation of cellular senescence and DNA integrity/damage checkpoint, which are commonly enriched pathways, 21 genes were down-regulated and directly related to DNA repair. Compared to the endometriosis samples, some chlamydial endometritis samples presented a lack of enriched immune pathways. Our results suggest that both conditions show similar distributions of microenvironment cell types, the downregulation of genes involved in DNA repair and cell cycle control, and pathways involved in immune response evasion.
本研究旨在考虑组织微环境异质性、转录基因谱和富集途径,确定子宫内膜异位症患者的在位内膜与衣原体引起的子宫内膜炎之间的关键相似性。对包括腺体和基质子宫内膜成分的样本进行了全转录组微阵列的荟萃分析,使用了包括样本在内的公开可用数据。对照样本来自没有任何报告的病理状况的女性。仅包括在增殖期月经期间获得的样本。使用一种集成基因集富集和去卷积方法的方法预测细胞组织异质性。通过主成分分析和经验贝叶斯方法估计批次效应。使用调整后的 p 值 < 0.05 和倍数变化 = 1.5 识别差异表达基因。使用 STRING 数据库和超过 400 的交互得分构建蛋白质-蛋白质相互作用网络。使用分子特征数据库进行功能富集分析。两种情况在微环境中的细胞类型方面都显示出相似性,特别是 CD4 和 CD8 Tem 细胞、NKT 细胞、Th2 细胞、嗜碱性粒细胞和嗜酸性粒细胞。关于细胞衰老和 DNA 完整性/损伤检查点的调节,这些是常见的富集途径,有 21 个基因下调,与 DNA 修复直接相关。与子宫内膜异位症样本相比,一些衣原体子宫内膜炎样本缺乏富集的免疫途径。我们的研究结果表明,两种情况都显示出相似的微环境细胞类型分布,与 DNA 修复和细胞周期控制相关的基因下调,以及参与免疫反应逃避的途径。