{"paper_id":"92c98d16-24d0-45b7-add3-20bd660e298f","body_text":"Abstract\nBackground\nExtracellular vesicles (EVs), including exosomes, play pivotal roles in the pathogenesis, diagnosis, and treatment of endometriosis. These nanosized vesicles carry bioactive molecules such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs), proteins, and lipids, facilitating intercellular communication and modulating the mechanisms that drive disease progression. This systematic review aims to synthesize the current evidence on the role of EVs in the pathophysiology of endometriosis, their potential as diagnostic biomarkers, and their therapeutic applications.\nMethods\nA comprehensive systematic review was conducted following the PRISMA guidelines. A systematic search of PubMed, Web of Science, Embase, and Scopus was performed for studies published between 2019 and 2024. The search terms included “extracellular vesicles” AND “endometriosis”, “pathogenesis” AND “diagnostic biomarkers” AND “therapeutic potential” AND “targeted therapy”. After screening 327 records, 269 unique studies were assessed. Following a full-text review of the remaining articles, 43 studies were included in the qualitative synthesis.\nResults\nOur review identified critical roles of EVs in immune modulation, epithelial-mesenchymal transition (EMT), and fertility impairment, all of which contribute to the progression of endometriosis. EVs carry molecular cargo that mirrors disease pathophysiology, highlighting their potential as noninvasive biomarkers for early diagnosis and disease monitoring. Additionally, engineered EVs offer novel therapeutic strategies for targeting disease-specific pathways.\nConclusions\nThis review highlights the multifaceted roles of EVs in endometriosis. EV-derived biomarkers, particularly miRNAs and proteins, show promise for noninvasive diagnosis and disease monitoring, while engineered EVs hold potential for targeted therapeutic interventions. These findings highlight the transformative potential of EVs in the diagnosis, prognosis, and treatment of endometriosis.\nGraphical abstract\nSchematic representation of the systematic review methodology and key findings on the role of extracellular vesicles in endometriosis. Fifty-two studies were ultimately included through databases such as Web of Science, Scopus, PubMed, and Embase, following PRISMA guidelines. The figure highlights the involvement of EVs in endometriosis pathogenesis (e.g., epithelial‒mesenchymal transition, inflammation, and fertility disruption), their potential as diagnostic biomarkers, and their therapeutic applications, including engineered EVs for targeted therapy and immune modulation.\nSimilar content being viewed by others\nData availability\nAll the data analyzed in this systematic review are included in the manuscript and its supplementary files. The datasets supporting the conclusions are derived from publicly available studies cited in the references.\nAbbreviations\n- EVs:\n-\nExtracellular vesicles\n- miRNAs:\n-\nmicroRNAs\n- lncRNAs:\n-\nlong noncoding RNAs\n- EMT:\n-\nepithelial-to-mesenchymal transition\n- PRISMA:\n-\nPreferred Reporting Items for Systematic Reviews and Meta-Analyses\n- MSCs:\n-\nMesenchymal stem cells\n- hUC-MSCs:\n-\nHuman Umbilical Cord Mesenchymal Stem Cells\n- ESC:\n-\nEndometrial Stromal Cell\n- MMP9:\n-\nMatrix metalloproteinase 9\n- PI3K/AKT:\n-\nPhosphoinositide 3-kinase/protein kinase B\n- TNF-α:\n-\ntumor necrosis factor\n- IL1B:\n-\nInterleukin 1 beta\n- ROS:\n-\nReactive oxygen species\n- TIMP3:\n-\nTissue Inhibitor of Metalloproteinases 3\n- DLL4/Notch:\n-\nDelta-like Ligand 4/Notch Signaling Pathway\n- BMSCs:\n-\nBone marrow mesenchymal stem cells\n- HOTAIR:\n-\nHOX transcript antisense RNA\n- STAT3:\n-\nSignal Transducer and Activator of Transcription 3\n- ANXA2:\n-\nAnnexin A2\nReferences\nSahraei SS et al (2022) A Comparative Study of Gene Expression in Menstrual Blood-Derived Stromal Cells between Endometriosis and Healthy Women. 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After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the publication’s content.\nFunding\nThis research received a specific grant (Grant number: 3734) from the Qom University of Medical Sciences.\nAuthor information\nAuthors and Affiliations\nContributions\nMohsen Sheykhhasan: Conceptualization, data curation, formal analysis, supervision, project administration, writing – original draft. Saeedeh Zare Jalise: Conceptualization, data curation, formal analysis, supervision, project administration, writing – original draft. Hourieh Kalhor: Methodology, Validation, Writing – review & editing. Tahereh Komeili Movahed: Investigation, Visualization, Writing – review & editing. Fatemeh Javaheri Tehrani: Writing – review & editing, final approval of the version to be published. Hamed Afkhami: Conceptualization, data curation, formal analysis, supervision, project administration, writing – original draft. All the authors read and approved the final manuscript.\nCorresponding authors\nEthics declarations\nCompeting interests\nThe authors declare no competing interests.\nConsent for publication\nNot applicable. The manuscript does not contain individual persons’ data in any form.\nEthics approval and consent to participate\nThis study was approved by the Qom University of Medical Sciences ethics committee (IR.MUQ.REC.1404.003).\nClinical trial number\nNot applicable.\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\nSheykhhasan, M., Zare Jalise, S., Kalhor, H. et al. The role of extracellular vesicles in endometriosis: A systematic review of pathogenesis, diagnostic biomarkers, and therapeutic potential. Mol Biol Rep 53, 452 (2026). https://doi.org/10.1007/s11033-026-11594-4\nReceived:\nAccepted:\nPublished:\nVersion of record:\nDOI: https://doi.org/10.1007/s11033-026-11594-4","source_license":"public-domain-us","license_restricted":false}