Differential gene expression profiling of ectopic endometrium reveals key molecular pathways in endometriosis pathogenesis

Background Endometriosis 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.

This 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.

A 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.

This study highlights coordinated dysregulation of epigenetic, inflammatory, angiogenic, and hormonal pathways in ectopic endometrial tissues, contributing to the molecular pathogenesis of endometriosis. While these findings provide insight into disease-associated molecular networks, further validation in larger and independent cohorts is required to clarify their biological and clinical relevance. Similar content being viewed by others Data availability The datasets generated and/or analysed during the current study are not publicly available due to institutional data-sharing restrictions and ongoing analyses but are available from the corresponding author upon reasonable request.

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We want to extend our sincere gratitude to Seed Grant (IoE, BHU) and Multi-Disciplinary Research Units (MRUs) Laboratory, a grant by ICMR-Department of Health Research. Funding Not available. Author information Authors and Affiliations Contributions RS, SR and GR conceived and designed the project. AA, SM and SS performed all operations. 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. Corresponding author Ethics declarations Consent for publication Not applicable. Competing interests The authors declare no competing interests. Institutional review board statement The 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). Consent to participate All research procedures were approved by and in accordance with relevant guidelines and regulations. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer 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. About this article Cite this article Rai, 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 Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s11033-026-11521-7