{"paper_id":"684b1efa-3cfd-4ecf-9b78-4c4c3be1b2a5","body_text":"Abstract\nAs a gynecological disease, endometriosis is a disease in which pain and inflammation are important parts. Endometriosis is a chronic, estrogen-related situation with a multifactorial etiology that remains incompletely understood. Endometriosis affects approximately 6–10% of females and is a prominent reason of infertility. Despite being histologically benign, endometriosis displays invasive behaviors and is associated with systemic inflammatory responses and immune dysfunction. In this text, endometriosis pathogenesis and pain associated with endometriosis is comprehensively explored with particular emphasis on inflammation, pain mechanisms and the emerging role of stem cells. Several theories, including coelomic metaplasia, lymphovascular dissemination, retrograde menstruation, and embryonic rest theory have been recommended to clarify the ectopic location of endometrial tissue. Among these, the immune-mediated inflammatory microenvironment and aberrant neurogenesis are considered in disease progression and the development of pain. The multifactorial nature of endometriosis-associated pain—encompassing inflammatory, neuropathic, and oxidative stress-related mechanisms—highlights the limitations of hormonal treatments and the necessity for new therapeutic perspectives. In this respect, the involvement of stem cells, particularly endometrial and mesenchymal stem cells, has attracted growing interest. These cells are implicated not only in the pathophysiology of the disease but also show promise in regenerative and immunomodulatory therapies. This review aims to present an integrative perspective on endometriosis by examining recent evidence on inflammatory signaling, neuroimmune alterations, and stem cell biology. A deeper understanding of these mechanisms may open new avenues for personalized and multidisciplinary treatment strategies in endometriosis management.\nSimilar content being viewed by others\nData availability\nNo datasets were generated or analysed during the current study.\nAbbreviations\n- NK:\n-\nNatural Killer\n- MUC5B:\n-\nMucin 5B\n- NRG1:\n-\nNeuregulin 1\n- ERBB3:\n-\nErb-B2 Receptor Tyrosine Kinase 3\n- IL:\n-\nInterleukin\n- PG:\n-\nProstaglandin\n- NGF:\n-\nNerve Growth Factor\n- TNF-α:\n-\nTumor Necrosis Factor-Alpha\n- ROS:\n-\nReactive Oxygen Species\n- miR:\n-\nMicroRNA\n- CD:\n-\nCluster of Differentiation\n- LGR5:\n-\nLeucine Rich Repeat Containing G-Protein Coupled Receptor 5\n- NKT:\n-\nNatural Killer T\n- SELL:\n-\nSelectin L\n- PDGF-Rβ:\n-\nPlatelet Derived Growth Factor-Receptor Beta\n- ITGAX:\n-\nIntegrin Subunit Alpha X\n- FGFBP2:\n-\nFibroblast Growth Factor Binding Protein 2\n- FCGR3A:\n-\nFc Gamma Receptor IIIa\n- DIE:\n-\nDeep Infiltrating Endometriosis\n- KIR:\n-\nKiller Cell Immunoglobulin Like Receptor\n- NT:\n-\nNeurotrophin\n- BDNF:\n-\nBrain-Derived Neurotrophic Factor\n- Lct:\n-\nLactase\n- TSG-6:\n-\nTumor Necrosis Factor-Stimulated Gene-6\n- LDL:\n-\nLow Density Lipoprotein\n- PTGES3:\n-\nProstaglandin E Synthase 3\n- NF-κβ:\n-\nNuclear Factor Kappa Beta\n- ATP:\n-\nAdenosine Triphosphate\n- ADP:\n-\nAdenosine Diphosphate\n- P2X3:\n-\nP2X Ligand-Gated Ion Channel 3\n- ADA:\n-\nAdenosine Deaminase\n- ENPP1:\n-\nEcto-Nucleotide Pyrophosphatase/Phosphodiesterase 1\n- NSAID:\n-\nNon-Steroidal Anti-Inflammatory Drugs\n- H + BSO:\n-\nHysterectomy with a Bilateral Salpingo-Oophorectomy\n- SC:\n-\nStem Cell\n- PSC:\n-\nPluripotent Stem Cell\n- MSC:\n-\nMesenchymal Stem Cell\n- BMSC:\n-\nBone Marrow-Derived Mesenchymal Stem Cell\n- ASC:\n-\nAdipose Tissue-Derived Stem Cell\n- VEGF-A:\n-\nVascular Endothelial Growth Factor-A\n- NAC:\n-\nN-acetylcysteine\n- HGF-1:\n-\nHepatocyte Growth Factor-1\n- HLA:\n-\nHuman Leukocyte Antigen\n- hEDSC:\n-\nHuman Endometrial-Derived Stem Cell\n- ESC:\n-\nEndometrial Stem Cell\n- eMSC:\n-\nEndometrial Mesenchymal Stem Cell\n- SP:\n-\nSide Population\n- MenSC:\n-\nMenstrual Stem Cell\n- MCP-1:\n-\nMonocyte Chemoattractant Protein-1\n- MCAM:\n-\nMelanoma Cell Adhesion Molecule\n- SSEA-1:\n-\nStage-Specific Embryonic Antigen-1\n- DNA:\n-\nDeoxyribonucleic Acid\n- eMSC:\n-\nEndometrial Mesenchymal Stem Cell\n- SUSD2:\n-\nSushi Domain Containing-2\n- CXCL8:\n-\nC-X-C-Motif Chemokine Ligand 8\n- TGF-β1:\n-\nTransforming Growth Factor-Beta 1\n- ICAM-1:\n-\nIntercellular Adhesion Molecule-1\n- SALL4:\n-\nSpalt Like Transcription Factor 4\n- LT:\n-\nLeukotriene\n- SOX2:\n-\nSRY-Box Transcription Factor 2\n- TX:\n-\nThromboxane\n- IFN-γ:\n-\nInterferon Gamma\n- ABCG2:\n-\nATP-Binding Cassette Transporter G2. SF-1:Steroidogenic Factor 1\n- HOXA10:\n-\nHomeobox A10\n- EMT:\n-\nEpithelial-Mesenchymal Transition\n- MAPK:\n-\nMitogen-Activated Protein Kinase\n- APC:\n-\nAntigen-Presenting Cell\n- TNF-β:\n-\nTumor Necrosis Factor-Beta\n- GM-CSF:\n-\nGranulocyte-Macrophage Colony-Stimulating Factor\n- CGRP:\n-\nCalcitonin Gene-Related Peptide\n- MC:\n-\nMast Cell\n- KIR2DL1:\n-\nKiller Cell Immunoglobulin Like Receptor, Two Ig Domains And Long Cytoplasmic Tail 1\n- MMP:\n-\nMatrix Metalloproteinase\n- COX-2:\n-\nCyclooxygenase-2\nReferences\nSasson IE, Hugh ST (2008) Stem cells and the pathogenesis of endometriosis. Ann N Y Acad Sci. https://doi.org/10.1196/annals.1434.014\nHufnagel D, Li F, Cosar E, Krikun G, Taylor HS (2015) The role of stem cells in the etiology and pathophysiology of endometriosis. 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Biomedicines. https://doi.org/10.3390/biomedicines11010039\nFunding\nThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\nAuthor information\nAuthors and Affiliations\nContributions\nAuthor ContributionsAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [H.A.]. Evaluation of the manuscript, detailed examination and supervision were performed by [H.E.]. The first draft of the manuscript was written by [H.A.] and all authors commented on previous versions of the manuscript. 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Mol Biol Rep 52, 860 (2025). https://doi.org/10.1007/s11033-025-10973-7\nReceived:\nAccepted:\nPublished:\nVersion of record:\nDOI: https://doi.org/10.1007/s11033-025-10973-7","source_license":"public-domain-us","license_restricted":false}