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Currently, no effective early diagnostic methods are available for early stages of endometriosis. We used menstrual fluid\u2010derived small extracellular vesicles (MF\u2010sEVs) from women with self\u2010reported endometriosis (laparoscopically diagnosed, <jats:italic>n<\/jats:italic> = 8) and self\u2010reported without endometriosis and no painful periods (<jats:italic>n<\/jats:italic> = 9). MF\u2010sEVs were separated using differential ultracentrifugation and characterised using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), Western Blot, flow cytometry, mass\u2010proteomics analysis and functional assays. Spherical\u2010shaped sEVs were identified with a median diameter of \u223c120\u00a0nm, expressing sEV marker proteins. The MF\u2010sEV proteins were classified as endometrial origin. Over 5000 proteins were identified, \u223c77% of which were decreased whilst only 22 proteins (largely comprising immunoglobulins) were increased in endometriosis\/MF\u2010sEVs compared to control\/MF\u2010sEVs. Decreased proteins were involved in nitrogen compound metabolism, immune response, intracellular signal transduction, regulation of programmed cell death, maintenance of cell polarity and actin cytoskeleton organisation. Flow cytometry demonstrated a significant increase in CD86 expression (immune activation marker) in endometriosis\/MF\u2010sEVs. Mesothelial cells showed a significant decrease in cellular resistance and junctional protein expression. MF\u2010sEVs are possible contributors to the pathogenesis of endometriosis and may have the potential for early detection of the disease.<\/jats:p>","DOI":"10.1002\/jev2.70048","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T03:07:41Z","timestamp":1742180861000},"source":"Crossref","is-referenced-by-count":9,"title":["Potential Role of Menstrual Fluid\u2010Derived Small Extracellular Vesicle Proteins in Endometriosis Pathogenesis"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9003-652X","authenticated-orcid":false,"given":"Shanti","family":"Gurung","sequence":"first","affiliation":[{"name":"The Ritchie Centre Hudson Institute of Medical Research  Clayton Australia"},{"name":"Obstetrics and Gynaecology Monash University  Clayton Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Piskopos","sequence":"additional","affiliation":[{"name":"The Ritchie Centre Hudson 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