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Given the importance of extracellular vesicles (EVs) in intercellular communication, we investigated how their protein landscape is reprogrammed and dysregulated during decidual response. Small EVs (sEVs) from human ESC-conditioned media at Day-2 and -14 following decidual stimuli were grouped as well- (WD) or poorly decidualized (PD) based on their prolactin secretion and subjected to mass spectrometry-based quantitative proteomics. On Day 2, in PD- versus WD-ESC-sEVs, 17 sEV- proteins were down-regulated (C5, C6; complement\/coagulation cascades, and SERPING1, HRG; platelet degranulation and fibrinolysis) and 39 up-regulated (FLNA, COL1A1; focal adhesion, ENO1, PKM; glycolysis\/gluconeogenesis, and RAP1B, MSN; leukocyte transendothelial migration). On Day 14, in PD- versus WD-ESC-sEVs, FLNA was down-regulated while 21 proteins were up-regulated involved in complement\/coagulation cascades (C3, C6), platelet degranulation (SERPINA4, ITIH4), B-cell receptor signalling and innate immune response (immunoglobulins). Changes from Days 2 to 14 suggested a subsequent response in PD-ESC-sEVs with 89 differentially expressed proteins mostly involved in complement and coagulation cascades (C3, C6, C5), but no change in WD-ESC-sEVs ESC. Poor decidualization was also associated with loss of crucial sEV-proteins for cell adhesion and invasion (ITGA5, PFN1), glycolysis (ALDOA, PGK1) and cytoskeletal reorganization (VCL, RAC1). Overall, this study indicates varied ESC response even prior to decidualization and provides insight into sEVs-proteomes as a benchmark of well-decidualized ESC. It shows distinct variation in sEV-protein composition depending on the ESC decidual response that is critical for embryo implantation, enabling and limiting trophoblast invasion during placentation and sensing a healthy embryo.<\/jats:p>","DOI":"10.1093\/molehr\/gaab057","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T07:12:43Z","timestamp":1631257963000},"source":"Crossref","is-referenced-by-count":23,"title":["The proteomes of endometrial stromal cell-derived extracellular vesicles following a decidualizing stimulus define the cells\u2019 potential for decidualization success"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9003-652X","authenticated-orcid":false,"given":"Shanti","family":"Gurung","sequence":"first","affiliation":[{"name":"Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, Victoria, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash Health, 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Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia"},{"name":"Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi Hui","family":"Poh","sequence":"additional","affiliation":[{"name":"Molecular Proteomics, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia"},{"name":"Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3300-8127","authenticated-orcid":false,"given":"Jemma","family":"Evans","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, Victoria, Australia"},{"name":"Department of Physiology, Monash University, Clayton, Victoria, 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