{"paper_id":"8991c123-d646-4f85-8ccf-16b659320028","body_text":"Abstract\nBackground\nEndometriosis is a chronic, estrogen-dependent inflammatory disease characterized by the presence of endometrial-like tissue outside the uterine cavity and is associated with pain, infertility, and impaired quality of life. Although its etiology is multifactorial, the molecular mechanisms underlying lesion establishment and persistence remain incompletely understood.\nMethods\nThis study investigated differential gene expression in ectopic endometrial tissues obtained from women with surgically and histologically confirmed endometriosis, compared with eutopic endometrium from healthy fertile controls. Targeted quantitative real-time PCR was performed to evaluate genes involved in epigenetic regulation, inflammation, angiogenesis, extracellular matrix remodeling, developmental pathways, and hormone signaling. Bioinformatics analyses, including Gene Ontology (GO) enrichment and protein–protein interaction (PPI) network analysis, were applied to elucidate functional pathways and gene interaction networks. Clinical and biochemical parameters were correlated with disease severity classified according to the revised American Society for Reproductive Medicine (rASRM) staging system.\nResults\nA total of 35 differentially expressed genes were identified, comprising 18 upregulated and 17 downregulated genes. Upregulated genes were predominantly associated with DNA methylation, inflammatory signaling, and angiogenesis, including DNMT1, DNMT3A, VEGFA, IL6, TNF-α, and MMP9, whereas downregulated genes included developmental and hormone-responsive regulators such as HOXA10, HOXA11, ESR1, PGR, and FOXO1. GO analysis revealed significant enrichment of epigenetic modification, immune response, and extracellular matrix organization among upregulated genes, while downregulated genes were enriched in developmental and transcriptional regulatory processes. PPI network analysis identified key hub genes within interconnected functional modules. Clinical and biochemical parameters, including serum CA-125 and CRP, increased progressively with rASRM stage.\nConclusion\nThis study highlights coordinated dysregulation of epigenetic, inflammatory, angiogenic, and hormonal pathways in ectopic endometrial tissues, contributing to the molecular pathogenesis of endometriosis. 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AA, SS analyzed the data and drew the figures. SM and AA wrote the manuscript. RS, SR and GR revised the manuscript. All authors contributed to the article and approved the submitted version.\nCorresponding author\nEthics declarations\nConsent for publication\nNot applicable.\nCompeting interests\nThe authors declare no competing interests.\nInstitutional review board statement\nThe study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of Institutional Ethical Committee, Institute of Medical Sciences, Banaras Hindu University (protocol code No. Dean/2021/EC/2397 and date of approval 15 February 2021).\nConsent to participate\nAll research procedures were approved by and in accordance with relevant guidelines and regulations.\nAdditional information\nPublisher’s note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nRai, G., Ashish, A., Rai, S. et al. Differential gene expression profiling of ectopic endometrium reveals key molecular pathways in endometriosis pathogenesis. Mol Biol Rep 53, 351 (2026). https://doi.org/10.1007/s11033-026-11521-7\nReceived:\nAccepted:\nPublished:\nVersion of record:\nDOI: https://doi.org/10.1007/s11033-026-11521-7","source_license":"public-domain-us","license_restricted":false}