Platelets as key cells in endometriosis patients: Insights from small extracellular vesicles in peritoneal fluid and endometriotic lesions analysis

血小板是子宫内膜异位症患者的关键细胞:从腹膜液中的小细胞外囊泡和子宫内膜异位症病变分析中获得的见解

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作者:Barbara Bortot, Roberta Di Florio, Simona Merighi, Ben Peacock, Rebecca Lees, Francesco Valle, Marco Brucale, Alessandro Mangogna, Giovanni Di Lorenzo, Federico Romano, Gabriella Zito, Fabrizio Zanconati, Giuseppe Ricci, Valeria Cancila, Beatrice Belmonte, Stefania Biffi

Abstract

Endometriosis is a chronic inflammatory condition characterized by the presence of endometrium-like tissue outside the uterus, primarily affecting pelvic organs and tissues. In this study, we explored platelet activation in endometriosis. We utilized the STRING database to analyze the functional interactions among proteins previously identified in small extracellular vesicles (EVs) isolated from the peritoneal fluid of endometriosis patients and controls. The bioinformatic analysis indicated enriched signaling pathways related to platelet activation, hemostasis, and neutrophil degranulation. Double immunohistochemistry analysis for CD61 and MPO revealed a significant presence of neutrophils and platelets in close contact infiltrating endometriotic lesions, suggesting potential cell-cell interactions. Subsequently, we isolated small EVs from the peritoneal fluid of women diagnosed with endometriosis and from women without endometriosis who underwent surgery for non-inflammatory benign diseases. We performed single-particle phenotyping analysis based on platelet biomarkers GPIIb/IIIa and PF4 using nanoflow cytometry, as well as single-particle morphological and nanomechanical characterization through atomic force microscopy. The study demonstrated that patients with endometriosis had a notably higher proportion of particles testing positive for platelet biomarkers compared to the total number of EVs. This finding implies a potential role for platelets in the pathogenesis of endometriosis. Further research is necessary to delve into the mechanisms underlying this phenomenon and its implications for disease progression.

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