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Although endometrial extracellular vesicles (EVs) are known to signal to the embryo during implantation, the role of embryo\u2010derived EVs remains largely unknown. Here, we provide a comprehensive proteomic characterisation of a major class of EVs, termed small EVs (sEVs), released by human trophectoderm cells (Tsc\u2010sEVs) and their capacity to reprogram protein landscape of endometrial epithelium in vitro. Highly purified Tsc\u2010sEVs (30\u2013200 nm, ALIX\n                    <jats:sup>+<\/jats:sup>\n                    , TSG101\n                    <jats:sup>+<\/jats:sup>\n                    , CD9\/63\/81\n                    <jats:sup>+<\/jats:sup>\n                    ) were enriched in known players of implantation (LIFR, ICAM1, TAGLN2, WNT5A, FZD7, ROR2, PRICKLE2), antioxidant activity (SOD1, PRDX1\/4\/6), tissue integrity (EZR, RAC1, RHOA, TNC), and focal adhesions (FAK, ITGA2\/V, ITGB1\/3). Functionally, Tsc\u2010sEVs were taken up by endometrial cells, altered transepithelial electrical resistance, and upregulated proteins implicated in embryo attachment (ITGA2\/V, ITGB1\/3), immune regulation (CD59, CD276, LGALS3), and antioxidant activity (GPX1\/3\/4, PRDX1\/2\/4\/5\/6): processes that are critical for successful implantation. Collectively, we provide critical insights into Tsc\u2010sEV\u2010mediated regulation of endometrial function that contributes to our understanding of the molecular basis of implantation.\n                  <\/jats:p>","DOI":"10.1002\/pmic.202000210","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T18:05:48Z","timestamp":1618596348000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Proteome reprogramming of endometrial epithelial cells by human trophectodermal small extracellular vesicles reveals key insights into embryo implantation"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2620-2834","authenticated-orcid":false,"given":"Qi Hui","family":"Poh","sequence":"first","affiliation":[{"name":"Baker Heart and Diabetes Institute Molecular Proteomics  Melbourne Victoria Australia"},{"name":"Department of Biochemistry and Genetics La Trobe Institute for Molecular Science La Trobe University  Bundoora Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7994-5151","authenticated-orcid":false,"given":"Alin","family":"Rai","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute Molecular Proteomics  Melbourne Victoria Australia"},{"name":"Central Clinical School Monash University  Melbourne Victoria Australia"},{"name":"Baker Department of Cardiometabolic Health University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irena I\u015bka","family":"Carmichael","sequence":"additional","affiliation":[{"name":"Monash Micro Imaging Monash Central Clinical School Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0558-7325","authenticated-orcid":false,"given":"Lois A","family":"Salamonsen","sequence":"additional","affiliation":[{"name":"Hudson Institute of Medical Research  Clayton Victoria Australia"},{"name":"Department of Molecular and Translational Science Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7516-485X","authenticated-orcid":false,"given":"David W","family":"Greening","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute Molecular Proteomics  Melbourne Victoria Australia"},{"name":"Department of Biochemistry and Genetics La Trobe Institute for Molecular Science La Trobe University  Bundoora Victoria Australia"},{"name":"Central Clinical School Monash University  Melbourne Victoria Australia"},{"name":"Baker Department of Cardiometabolic Health University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.12717\/DR.2017.21.4.351"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001200202"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.02.009"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2000-12565"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/des330"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2004.02.006"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.1.33"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/2.5.355"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(03)00772-6"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2015.09.003"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/det058"},{"issue":"1","key":"e_1_2_9_13_1","first-page":"10","article-title":"Molecular aspects of direct LH\/hCG effects on human endometrium\u2013lessons from intrauterine microdialysis in the human female in vivo","volume":"1","author":"Licht P.","year":"2001","journal-title":"Reproductive Biology"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0380"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.3.1047"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21051584"},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","unstructured":"Mohamed O. 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