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The precise mechanisms that dictate intercellular communications among the uterine cells during early pregnancy remain unknown. We recently reported that conditional deletion of the gene encoding the hypoxia-inducible transcription factor 2 alpha (Hif2\u03b1) in mouse uterus led to infertility. Here, we report that HIF2\u03b1 in mouse endometrial stromal cells (MESCs) acts via the cellular trafficking regulator RAB27b to control the secretion of extracellular vesicles (EVs) during decidualization. We also found that Hif2\u03b1-regulated pathways influence the biogenesis of EVs. Proteomic analysis of EVs secreted by decidualizing MESCs revealed that they harbor a wide variety of protein cargoes whose composition changed as the decidualization process progressed. The EVs enhanced the differentiation capacity of MESCs and the production of angiogenic factors by these cells. We also established that matrix metalloproteinase-2, a prominent EV cargo protein, modulates uterine remodeling during decidualization. Collectively, our results support the concept that EVs are central to the mechanisms by which the decidual cells communicate with each other and other cell types within the uterus to facilitate successful establishment of pregnancy.<\/jats:p>","DOI":"10.1210\/endocr\/bqac165","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T10:56:31Z","timestamp":1665485791000},"source":"Crossref","is-referenced-by-count":17,"title":["Extracellular Vesicles Secreted by Mouse Decidual Cells Carry Critical Information for the Establishment of Pregnancy"],"prefix":"10.1210","volume":"163","author":[{"given":"Qiuyan","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Illinois , Urbana-Champaign, Urbana, IL 61801 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob R","family":"Beal","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Illinois , Urbana-Champaign, Urbana, IL 61801 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangning","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Illinois , Urbana-Champaign, Urbana, IL 61801 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpita","family":"Bhurke","sequence":"additional","affiliation":[{"name":"Carle Woese Institute of Genomic Biology, University of Illinois , Urbana-Champaign, Urbana, IL 61801 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indrani C","family":"Bagchi","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences, University of Illinois , Urbana-Champaign, Urbana, IL 61802 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0371-2463","authenticated-orcid":false,"given":"Milan 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