{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T16:12:38Z","timestamp":1786378358164,"version":"build-2736575974"},"reference-count":102,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Intercellular communication is essential for healthy embryo development, yet the role and dynamics of extracellular space in the maternal\u2010embryonic dialogue remain unclear. Furthermore, little is known of maternal and embryonic metabolic states during early endometrial preparation and after the embryo enters the uterine cavity. Using a human in vitro co\u2010culture model and extracellular vesicle (EV)\u2010specific tools, we dynamically tracked EV secretion, uptake and processing between embryonic and endometrial cells at early stages of cell\u2010to\u2010cell communication. Hormonal stimulation altered endometrial secretory output, producing distinct EV populations. Stimulated EVs (St\u2010EVs) differed from non\u2010stimulated EVs (NSt\u2010EVs) in size, secretion dynamics, uptake efficiency and metabolic cargo, selectively packaging energy\u2010related metabolites and aryl hydrocarbon receptor (AhR) ligands. AhR inhibition increased spheroid attachment, suggesting that AhR signalling regulates implantation by modulating the endometrial environment. Additionally, lipid droplets (LDs) affected by endometrial\u2010 and embryo\u2010derived EVs were actively secreted and taken up by embryonic cells, highlighting their role in implantation. EVs were not only exchanged between the embryo and endometrium but were also rapidly internalized, influencing mitochondrial activity, lipid metabolism and extracellular matrix remodelling. Translation of EV\u2010derived mRNA occurred within 1\u00a0h of uptake, driving cellular changes and enhancing embryo attachment. These findings suggest EVs, extracellular metabolites and LDs mobilized between the endometrium and embryo coordinate to promote embryo attachment and implantation. This study advances our understanding of embryo\u2010maternal EV\u2010mediated communication and provides a valuable model for investigating EV\u2010mediated simultaneous intercellular bidirectional crosstalk in other biological contexts.<\/jats:p>","DOI":"10.1002\/jev2.70161","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T11:28:47Z","timestamp":1762860527000},"source":"Crossref","is-referenced-by-count":4,"title":["Extracellular Vesicles, Lipid Droplets and AhR Ligands in Early Implantation: The Dynamics of Embryo\u2010Maternal Crosstalk"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9610-3674","authenticated-orcid":false,"given":"Alisa","family":"Komsky\u2010Elbaz","sequence":"first","affiliation":[{"name":"Department of Entomology The Hebrew University  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5519-1022","authenticated-orcid":false,"given":"Margarita","family":"Shuhmaher","sequence":"additional","affiliation":[{"name":"Department of Entomology The Hebrew University  Rehovot Israel"},{"name":"Current Address: Biomedical Engineering Technion Israel Institute of Technology  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4684-1238","authenticated-orcid":false,"given":"Javier Arturo","family":"Sanchez\u2010Lopez","sequence":"additional","affiliation":[{"name":"Department of Entomology The Hebrew University  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oria","family":"Teena","sequence":"additional","affiliation":[{"name":"Department of Entomology The Hebrew University  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6200-4867","authenticated-orcid":false,"given":"Daniel","family":"Waiger","sequence":"additional","affiliation":[{"name":"Center for Scientific Imaging The Hebrew University  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4048-1887","authenticated-orcid":false,"given":"Einat","family":"Zelinger","sequence":"additional","affiliation":[{"name":"Center for Scientific Imaging The Hebrew University  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7114-0703","authenticated-orcid":false,"given":"Tally","family":"Kossovsky","sequence":"additional","affiliation":[{"name":"Center for Scientific Imaging The Hebrew University  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7641-4873","authenticated-orcid":false,"given":"Leilah","family":"Otikovs","sequence":"additional","affiliation":[{"name":"Sciences Core Facilities Weizmann Institute  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eshel","family":"Dilevsky","sequence":"additional","affiliation":[{"name":"Markel Technologies\u00a0Ltd.  Yehud Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7662-5195","authenticated-orcid":false,"given":"Yoav","family":"Soen","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences Weizmann Institute  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5270-8954","authenticated-orcid":false,"given":"Amir","family":"Hefetz","sequence":"additional","affiliation":[{"name":"DataGraph  Holon Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6997-7704","authenticated-orcid":false,"given":"Yael","family":"Heifetz","sequence":"additional","affiliation":[{"name":"Department of Entomology The Hebrew University  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.125"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2017-00229"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20092162"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2022.01.011"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2021.10.007"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.115.134890"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.animal.2021.100182"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.202000210"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2021.12.015"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12101564"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.104.030957"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3978"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-12879-2"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00763-8"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-023-00576-0"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-05549-w"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.20517\/evcna.2023.18"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.5772\/intechopen.75168"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9767"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2013.08.011"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2012.03.010"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1078096"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dead138"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-021-00801-5"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2001.tb03792.x"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0378(01)00140-1"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-11-0484"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13036-020-00240-7"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-09-0271"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.181925"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31323-2"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/biosci\/biv084"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8029"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jex2.77"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2020.04.013"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep17217"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.3128"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15747-2"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201703206"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2010.01041.x"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24304"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01221-1"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202300710R"},{"key":"e_1_2_10_45_1","first-page":"1","article-title":"Extracellular Vesicles\u2010Coupled miRNAs From Oviduct and Uterus Modulate Signaling Pathways Related to Lipid Metabolism and Bovine Early Embryo Development","volume":"15","author":"Mazzarella R.","year":"2024","journal-title":"Journal of Animal Science and Biotechnology"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27894"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-19958-z"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00432"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202200677R"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn404945r"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(98)00437-3"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389557511313110007"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.2014.982533"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1MD00015B"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115544"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M804393200"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2003.10.022"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.107.061044"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-019-01670-z"},{"key":"e_1_2_10_60_1","first-page":"1","article-title":"Insights Into the Lipidome and Primary Metabolome of the Uterus From Day 14 Cyclic and Pregnant Sheep\u2020","volume":"2021","author":"O'Neil E. V.","year":"2021","journal-title":"Biology of Reproduction"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13020279"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2008.09.031"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2008.11.021"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15010151"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-024-01750-y"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03098"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.596324"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/rda.14320"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.45586"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.103.020651"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod56.2.409"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.19.11522"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2017.07.009"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01735-1"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.064246"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2020.07.011"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1356914"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1080\/13813455.2017.1398262"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-023-02904-x"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094644"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1530\/RAF-23-0016"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-019-00040-5"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.22037"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2021.06.022"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.656629"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M026732"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039463"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.107.061044"},{"key":"e_1_2_10_89_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmac026"},{"key":"e_1_2_10_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2013.04.011"},{"key":"e_1_2_10_91_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2018-00752"},{"key":"e_1_2_10_92_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.105361"},{"key":"e_1_2_10_93_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202001104R"},{"key":"e_1_2_10_94_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M600098-JLR200"},{"key":"e_1_2_10_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2018.03.001"},{"key":"e_1_2_10_96_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-2403"},{"key":"e_1_2_10_97_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.012841"},{"key":"e_1_2_10_98_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-011-1061-y"},{"key":"e_1_2_10_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.04.004"},{"key":"e_1_2_10_100_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124289"},{"key":"e_1_2_10_101_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11958"},{"key":"e_1_2_10_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2012.03.017"},{"key":"e_1_2_10_103_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-05549-w"}],"container-title":["Journal of Extracellular Vesicles"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jev2.70161","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T09:42:55Z","timestamp":1765186975000},"score":1,"resource":{"primary":{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/10.1002\/jev2.70161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":102,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/jev2.70161"],"URL":"https:\/\/doi.org\/10.1002\/jev2.70161","archive":["Portico"],"relation":{},"ISSN":["2001-3078","2001-3078"],"issn-type":[{"value":"2001-3078","type":"print"},{"value":"2001-3078","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"article-number":"e70161"}}