The role of extracellular vesicles in endometriosis: A systematic review of pathogenesis, diagnostic biomarkers, and therapeutic potential

Background Extracellular 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.

A 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.

Our 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.

This 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. Graphical abstract Schematic 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. Similar content being viewed by others Data availability All 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. Abbreviations - EVs: - Extracellular vesicles - miRNAs: - microRNAs - lncRNAs: - long noncoding RNAs - EMT: - epithelial-to-mesenchymal transition - PRISMA: - Preferred Reporting Items for Systematic Reviews and Meta-Analyses - MSCs: - Mesenchymal stem cells - hUC-MSCs: - Human Umbilical Cord Mesenchymal Stem Cells - ESC: - Endometrial Stromal Cell - MMP9: - Matrix metalloproteinase 9 - PI3K/AKT: - Phosphoinositide 3-kinase/protein kinase B - TNF-α: - tumor necrosis factor - IL1B: - Interleukin 1 beta - ROS: - Reactive oxygen species - TIMP3: - Tissue Inhibitor of Metalloproteinases 3 - DLL4/Notch: - Delta-like Ligand 4/Notch Signaling Pathway - BMSCs: - Bone marrow mesenchymal stem cells - HOTAIR: - HOX transcript antisense RNA - STAT3: - Signal Transducer and Activator of Transcription 3 - ANXA2: - Annexin A2

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The authors thank the researchers whose work was included in this systematic review. During the preparation of this work, the authors used ChatGPT via OpenAI to improve paper readability. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the publication’s content. Funding This research received a specific grant (Grant number: 3734) from the Qom University of Medical Sciences. Author information Authors and Affiliations Contributions Mohsen 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. Corresponding authors Ethics declarations Competing interests The authors declare no competing interests. Consent for publication Not applicable. The manuscript does not contain individual persons’ data in any form. Ethics approval and consent to participate This study was approved by the Qom University of Medical Sciences ethics committee (IR.MUQ.REC.1404.003). Clinical trial number Not applicable. 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 Sheykhhasan, 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 Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s11033-026-11594-4