{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T02:40:45Z","timestamp":1784860845692,"version":"3.55.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32172724"],"award-info":[{"award-number":["32172724"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Extracellular vesicles (EVs) are membrane-coating nanoparticles derived from cells. The effect of cell-to-cell communication mediated by EVs has been investigated in different fields of physio-logical as well as pathological process in recent years. Reproduction, regarded as a definitive characteristic of organisms, has been a focus in both animal and medical sciences. It is well agreed that implantation is a critical event during early pregnancy in viviparous animals, and a proper implantation is essential for the establishment and maintenance of normal pregnancy. However, successful implantation requires the synchronized development of both the uterus and the embryo, therefore, in which well communication and opportune regulation are necessary. This review focuses on the progression of studies that reveal the role of EVs in early pregnancy, especially during implantation. Based on current evidence, EVs are produced and exist in the environment for implantation. It has been proved that EVs of different origins such as endometrium and embryo, have positive influences on embryo implantation. With their cargos of proteins and nucleic acids (especially microRNAs), EVs exert their effects including information transportation, immune stimulation and regulation of gene expression.<\/jats:p>","DOI":"10.3389\/fendo.2022.809596","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T05:03:49Z","timestamp":1643346229000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":45,"title":["The Role of Extracellular Vesicles in Embryo Implantation"],"prefix":"10.3389","volume":"13","author":[{"given":"Kaiyu","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyong","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ti","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunchao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengguang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1997.tb52136.x","article-title":"Uterine Pinopodes in Peri-Implantation Human Endometrium. Clinical Relevance","volume":"816","author":"Nikas","year":"1997","journal-title":"Ann N Y Acad Sci"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.09.010","article-title":"Conditional Deletion of Msx Homeobox Genes in the Uterus Inhibits Blastocyst Implantation by Altering Uterine Receptivity","volume":"21","author":"Daikoku","year":"2011","journal-title":"Dev Cell"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199906103402304","article-title":"Time of Implantation of the Conceptus and Loss of Pregnancy","volume":"340","author":"Wilcox","year":"1999","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05938.x","article-title":"Inflammation and Pregnancy: The Role of the Immune System at the Implantation Site","volume":"1221","author":"Mor","year":"2011","journal-title":"Ann N Y Acad Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198807283190401","article-title":"Incidence of Early Loss of Pregnancy","volume":"319","author":"Wilcox","year":"1988","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"13525","DOI":"10.1038\/s41598-017-13683-8","article-title":"Micro-Ribonucleic Acids and Extracellular Vesicles Repertoire in the Spent Culture Media Is Altered in Women Undergoing In Vitro Fertilization","volume":"7","author":"Abu-Halima","year":"2017","journal-title":"Sci Rep"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v4.27066","article-title":"Biological Properties of Extracellular Vesicles and Their Physiological Functions","volume":"4","author":"Yanez-Mo","year":"2015","journal-title":"J Extracell Vesicles"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2012.03.006","article-title":"Tumor Cell-Derived Exosomes: A Message in a Bottle","volume":"1826","author":"Kharaziha","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"B9","doi-asserted-by":"publisher","first-page":"18","DOI":"10.5483\/BMBRep.2016.49.1.239","article-title":"Emerging Roles of Exosomes in Cancer Invasion and Metastasis","volume":"49","author":"Soung","year":"2016","journal-title":"BMB Rep"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090913","article-title":"Extracellular Vesicles in Luminal Fluid of the Ovine Uterus","volume":"9","author":"Burns","year":"2014","journal-title":"PloS One"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0158278","article-title":"Induction of IFNT-Stimulated Genes by Conceptus-Derived Exosomes During the Attachment Period","volume":"11","author":"Nakamura","year":"2016","journal-title":"PloS One"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.11.176","article-title":"Intrauterine Exosomes Are Required for Bovine Conceptus Implantation","volume":"495","author":"Kusama","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"B13","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1111\/j.1600-0897.2012.01109.x","article-title":"The Myxovirus-Resistance Protein, Mx1, is a Component of Exosomes Secreted by Uterine Epithelial Cells","volume":"67","author":"Racicot","year":"2012","journal-title":"Am J Reprod Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058502","article-title":"Endometrial Exosomes\/Microvesicles in the Uterine Microenvironment: A New Paradigm for Embryo-Endometrial Cross Talk at Implantation","volume":"8","author":"Ng","year":"2013","journal-title":"PloS One"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0196080","article-title":"Murine Embryos Exposed to Human Endometrial MSCs-Derived Extracellular Vesicles Exhibit Higher VEGF\/PDGF AA Release, Increased Blastomere Count and Hatching Rates","volume":"13","author":"Blazquez","year":"2018","journal-title":"PloS One"},{"key":"B16","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1095\/biolreprod.115.134890","article-title":"Human Endometrial Exosomes Contain Hormone-Specific Cargo Modulating Trophoblast Adhesive Capacity: Insights Into Endometrial-Embryo Interactions","volume":"94","author":"Greening","year":"2016","journal-title":"Biol Reprod"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1177\/1933719112450332","article-title":"Emmprin Is Secreted by Human Uterine Epithelial Cells in Microvesicles and Stimulates Metalloproteinase Production by Human Uterine Fibroblast Cells","volume":"19","author":"Braundmeier","year":"2012","journal-title":"Reprod Sci"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioy011","article-title":"Progesterone Effects on Extracellular Vesicles in the Sheep Uterus","volume":"98","author":"Burns","year":"2018","journal-title":"Biol Reprod"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2098","article-title":"Stimulation of Gpr30 Increases Release of Emmprin-Containing Microvesicles in Human Uterine Epithelial Cells","volume":"97","author":"Burnett","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"B20","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1095\/biolreprod.115.129296","article-title":"\u2018Conceptualizing\u2019 the Endometrium: Identification of Conceptus-Derived Proteins During Early Pregnancy in Cattle","volume":"92","author":"Forde","year":"2015","journal-title":"Biol Reprod"},{"key":"B21","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1095\/biolreprod.115.134973","article-title":"Extracellular Vesicles Originate From the Conceptus and Uterus During Early Pregnancy in Sheep","volume":"94","author":"Burns","year":"2016","journal-title":"Biol Reprod"},{"key":"B22","doi-asserted-by":"publisher","first-page":"5210","DOI":"10.1038\/s41598-017-05549-w","article-title":"Secretome of In Vitro Cultured Human Embryos Contains Extracellular Vesicles That Are Uptaken by the Maternal Side","volume":"7","author":"Giacomini","year":"2017","journal-title":"Sci Rep"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0178306","article-title":"Identification and Characteristics of Extracellular Vesicles From Bovine Blastocysts Produced In Vitro","volume":"12","author":"Mellisho","year":"2017","journal-title":"PloS One"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.23093","article-title":"Embryotrophic Effects of Extracellular Vesicles Derived From Outgrowth Embryos in Pre- and Peri-Implantation Embryonic Development in Mice","volume":"86","author":"Kim","year":"2019","journal-title":"Mol Reprod Dev"},{"key":"B25","doi-asserted-by":"publisher","first-page":"203","DOI":"10.3390\/genes11020203","article-title":"Identification and Characterization of Extracellular Vesicles and Its DNA Cargo Secreted During Murine Embryo Development","volume":"11","author":"Simon","year":"2020","journal-title":"Genes (Basel)"},{"key":"B26","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1038\/s41598-018-36452-7","article-title":"Identification of Extracellular Vesicles and Characterization of Mirna Expression Profiles in Human Blastocoel Fluid","volume":"9","author":"Battaglia","year":"2019","journal-title":"Sci Rep"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11958","article-title":"Microvesicles Provide a Mechanism for Intercellular Communication by Embryonic Stem Cells During Embryo Implantation","volume":"7","author":"Desrochers","year":"2016","journal-title":"Nat Commun"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0174535","article-title":"Effects of Embryo-Derived Exosomes on the Development of Bovine Cloned Embryos","volume":"12","author":"Qu","year":"2017","journal-title":"PloS One"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1089\/cell.2014.0003","article-title":"Improvement of Cloned Embryos Development by Co-Culturing With Parthenotes: A Possible Role of Exosomes\/Microvesicles for Embryos Paracrine Communication","volume":"16","author":"Saadeldin","year":"2014","journal-title":"Cell Reprogram"},{"key":"B30","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/s41598-019-57060-z","article-title":"Amniotic Microvesicles Impact Hatching and Pregnancy Percentages of In Vitro Bovine Embryos and Blastocyst Microrna Expression Versus In Vivo Controls","volume":"10","author":"Lange-Consiglio","year":"2020","journal-title":"Sci Rep"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaaa034","article-title":"Exosomes and Soluble Secretome From Hormone-Treated Endometrial Epithelial Cells Direct Embryo Implantation","volume":"26","author":"Gurung","year":"2020","journal-title":"Mol Hum Reprod"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098667","article-title":"A Gestational Profile of Placental Exosomes in Maternal Plasma and Their Effects on Endothelial Cell Migration","volume":"9","author":"Salomon","year":"2014","journal-title":"PloS One"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201800423","article-title":"Human Endometrial Extracellular Vesicles Functionally Prepare Human Trophectoderm Model for Implantation: Understanding Bidirectional Maternal-Embryo Communication","volume":"19","author":"Evans","year":"2019","journal-title":"Proteomics"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1530\/REP-18-0616","article-title":"Decidual Small Extracellular Vesicles Induce Trophoblast Invasion by Upregulating N-Cadherin","volume":"159","author":"Liu","year":"2019","journal-title":"Reproduction"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1530\/REP-14-0538","article-title":"Exosomes, Endogenous Retroviruses and Toll-Like Receptors: Pregnancy Recognition in Ewes","volume":"149","author":"Ruiz-Gonzalez","year":"2015","journal-title":"Reproduction"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2019.02.010","article-title":"Seminal Exosomes Induce Interleukin-6 and Interleukin-8 Secretion by Human Endometrial Stromal Cells","volume":"235","author":"Paktinat","year":"2019","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deaa015","article-title":"Seminal Plasma Promotes Decidualization of Endometrial Stromal Fibroblasts In Vitro From Women With and Without Inflammatory Disorders in a Manner Dependent on Interleukin-11 Signaling","volume":"35","author":"George","year":"2020","journal-title":"Hum Reprod"},{"key":"B38","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1111\/j.1600-0897.2010.00880.x","article-title":"Trophoblast-Derived Exosomes Mediate Monocyte Recruitment and Differentiation","volume":"65","author":"Atay","year":"2011","journal-title":"Am J Reprod Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.repbio.2019.06.003","article-title":"Exosome-Derived Uterine Micrornas Isolated From Cows With Endometritis Impede Blastocyst Development","volume":"19","author":"Wang","year":"2019","journal-title":"Reprod Biol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.04.005","article-title":"Endometrial Extracellular Vesicles From Women With Recurrent Implantation Failure Attenuate the Growth and Invasion of Embryos","volume":"114","author":"Liu","year":"2020","journal-title":"Fertil Steril"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1530\/REP-19-0314","article-title":"Ifnt-Independent Effects of Intrauterine Extracellular Vesicles (Evs) in Cattle","volume":"159","author":"Nakamura","year":"2020","journal-title":"Reproduction"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2011.00995.x","article-title":"Human Trophoblast-Derived Exosomal Fibronectin Induces Pro-Inflammatory Il-1beta Production by Macrophages","volume":"66","author":"Atay","year":"2011","journal-title":"Am J Reprod Immunol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"4662","DOI":"10.1038\/s41598-018-23112-z","article-title":"Pibf+ Extracellular Vesicles From Mouse Embryos Affect Il-10 Production by Cd8+ Cells","volume":"8","author":"Pallinger","year":"2018","journal-title":"Sci Rep"},{"key":"B44","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s12958-017-0309-7","article-title":"Role of Micrornas in Embryo Implantation","volume":"15","author":"Liang","year":"2017","journal-title":"Reprod Biol Endocrinol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-018-1326-y","article-title":"The Role of Micrornas in Human Embryo Implantation: A Review","volume":"36","author":"Paul","year":"2019","journal-title":"J Assist Reprod Genet"},{"key":"B46","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1186\/s12964-019-0448-x","article-title":"Specific Trophoblast Transcripts Transferred by Extracellular Vesicles Affect Gene Expression in Endometrial Epithelial Cells and May Have a Role in Embryo-Maternal Crosstalk","volume":"17","author":"Es-Haghi","year":"2019","journal-title":"Cell Commun Signal"},{"key":"B47","doi-asserted-by":"publisher","first-page":"20330","DOI":"10.1038\/s41598-019-56879-w","article-title":"Effects of Mir-98 in Intrauterine Extracellular Vesicles on Maternal Immune Regulation During the Peri-Implantation Period in Cattle","volume":"9","author":"Nakamura","year":"2019","journal-title":"Sci Rep"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2020.10.043","article-title":"Endometrial Cell-Derived Small Extracellular Vesicle Mir-100-5p Promotes Functions of Trophoblast During Embryo Implantation","volume":"23","author":"Tan","year":"2021","journal-title":"Mol Ther Nucleic Acids"},{"key":"B49","doi-asserted-by":"publisher","first-page":"645","DOI":"10.3390\/cells9030645","article-title":"Micrornas in Small Extracellular Vesicles Indicate Successful Embryo Implantation During Early Pregnancy","volume":"9","author":"Tan","year":"2020","journal-title":"Cells"},{"key":"B50","doi-asserted-by":"publisher","first-page":"9862","DOI":"10.1038\/s41598-020-66872-3","article-title":"Identification of Core Genes in the Progression of Endometrial Cancer and Cancer Cell-Derived Exosomes by an Integrative Analysis","volume":"10","author":"Shi","year":"2020","journal-title":"Sci Rep"},{"key":"B51","doi-asserted-by":"publisher","first-page":"811","DOI":"10.3390\/cells8080811","article-title":"Clues to Non-Invasive Implantation Window Monitoring: Isolation and Characterisation of Endometrial Exosomes","volume":"8","author":"Luddi","year":"2019","journal-title":"Cells"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioy263","article-title":"Extracellular Vesicles Derived From Endometrial Human Mesenchymal Stem Cells Enhance Embryo Yield and Quality in an Aged Murine Model","volume":"100","author":"Marinaro","year":"2019","journal-title":"Biol Reprod"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.809596\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T05:03:51Z","timestamp":1643346231000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.809596\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,28]]},"references-count":52,"alternative-id":["10.3389\/fendo.2022.809596"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.809596","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,28]]},"article-number":"809596"}}