Transcriptome meta-analysis reveals differences of immune profile between eutopic endometrium from stage I-II and III-IV endometriosis independently of hormonal milieu

Omero Benedicto Poli-Neto, Omero Benedicto Poli‐Neto, Juliana Meola, Julio Cesar Rosa-E-Silva, Júlio César Rosa e Silva, Daniel Guimarães Tiezzi, Daniel Tiezzi
Scientific reports · 2020 · vol. 10(1) , pp. 313 · doi:10.1038/s41598-019-57207-y · PMID:31941945 · W3000127458
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

A meta-analysis found differences in immune cell profiles and enriched pathways in eutopic endometrium from women with endometriosis, varying by disease stage and independent of menstrual cycle phase.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

This study performed a transcriptome meta-analysis of publicly deposited whole-transcriptome microarray datasets from eutopic endometrium of women with stage I–II versus stage III–IV endometriosis and healthy controls, with analyses designed to be independent of menstrual cycle phase and hormonal milieu. After batch correction and differential expression/pathway enrichment, the authors found higher activated dendritic cells, CD4 T effector memory cells, eosinophils, M1 macrophages, and NKT cells in stage I–II endometriosis, while M2 macrophages and NKT cells were elevated in stage III–IV endometriosis; smooth muscle cells were more prevalent in healthy controls. Enriched pathways included immune surveillance, stem cell self-renewal, and epithelial–mesenchymal transition, with PI3K/AKT/mTOR, TGF signaling, and interferon α/γ responses enriched specifically in stage III–IV disease, and network-mapped genes (FOS, FOSB, JUNB, EGR1) consistent across stages and cycle phases. The paper’s major caveat is that conclusions are limited by reliance on existing microarray raw data and its selection criteria, even though meta-analysis was used to address technical variability and batch effects. This paper is centrally about endometriosis—meta-analyzing transcriptomic differences in immune-cell and pathway profiles in eutopic endometrium across disease stages.

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Abstract

Eutopic endometrium appears to be crucial for endometriosis development. Despite of the evident importance, data regarding the cellular microenvironment remain unclear. Our objective was to explore the tissue microenvironment heterogeneity, transcripts, and pathways that are enriched in all phases of the menstrual cycle by analysing publicly deposited data derived from whole transcriptome microarrays of eutopic endometria of women with and without endometriosis. A meta-analysis of the transcriptome microarrays was performed using raw data available from a public database. Eligibility criteria included eutopic endometrium samples from women with endometriosis and healthy controls without any pathological condition reported the presence of an adequately reported normal menstrual phase, and samples containing both glandular and stromal components. Raw data were processed using a robust multiarray average method to provide background correction, normalisation, and summarisation. The batch effect was estimated by principal variant component analysis and removed using an empirical Bayes method. Cellular tissue heterogeneity was inferred using the xCell package. Differentially expressed genes were identified based on a 5% adjusted p value and a 2.0-fold change. Pathways were identified by functional enrichment based on the Molecular Signatures Database, a p value of < 5%, and an FDR q value of ≤ 25%. Genes that were more frequently found in pathways were identified using leading edge analysis. In a manner independent of cycle phase, the subpopulations of activated dendritic cells, CD4 T effector memory phenotype cells, eosinophils, macrophages M1, and natural killer T cells (NKT) were all higher in stage I-II endometriosis compared to those in healthy controls. The subpopulations of M2 macrophages and natural killer T cells were elevated in eutopic endometriums from women with stage III-IV endometriosis, and smooth muscle cells were always more prevalent in healthy eutopic endometriums. Among the differently expressed genes, FOS, FOSB, JUNB, and EGR1 were the most frequently mapped within the interaction networks, and this was independent of stage and cycle phase. The enriched pathways were directly related to immune surveillance, stem cell self-renewal, and epithelial mesenchymal transition. PI3K AKT mTOR, TGF signalling, and interferon alpha/gamma responses were enriched exclusively in stage III-IV endometriosis. The cellular microenvironments and immune cell profiles were different between eutopic endometriums from women with stage I-II and stage III-IV endometriosis, and these differences were independent of the hormonal milieu. Specifically, a pro-inflammatory profile was predominant in stage I-II endometriosis, and M1-M2 polarization into eutopic endometrium may be crucial for the progression of the disease. The higher prevalence of NKT cells in eutopic endometriums from women with endometriosis that was independent of cycle phase or staging suggested a sustained stress and/or damage to these eutopic endometriums. Based on this, the results of this meta-analysis are important for identifying challenges and opportunities for future research.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Endometrium Transcriptome Adult Case-Control Studies Cellular Microenvironment Cluster Analysis Databases, Factual Endometriosis Endometriosis Endometriosis Endometrium Epithelial-Mesenchymal Transition Female Gene Expression Profiling Gene Expression Profiling Humans Phosphatidylinositol 3-Kinases Phosphatidylinositol 3-Kinases Principal Component Analysis

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