{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:42:25Z","timestamp":1793727745054,"version":"4.6.1"},"reference-count":64,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Decidualizing endometrial stromal cells (EnSC) critically determine the maternal response to an implanting conceptus, triggering either menstruation\u2010like disposal of low\u2010fitness embryos or creating an environment that promotes further development. However, the mechanism that couples maternal recognition of low\u2010quality embryos to tissue breakdown remains poorly understood. Recently, we demonstrated that successful transition of the cycling endometrium to a pregnancy state requires selective elimination of pro\u2010inflammatory senescent decidual cells by activated uterine natural killer (uNK) cells. Here we report that uNK cells express CD44, the canonical hyaluronan (HA) receptor, and demonstrate that high molecular weight HA (HMWHA) inhibits uNK cell\u2010mediated killing of senescent decidual cells. In contrast, low molecular weight HA (LMWHA) did not attenuate uNK cell activity in co\u2010culture experiments. Killing of senescent decidual cells by uNK cells was also inhibited upon exposure to medium conditioned by IVF embryos that failed to implant, but not successful embryos. Embryo\u2010mediated inhibition of uNK cell activity was reversed by recombinant hyaluronidase 2 (HYAL2), which hydrolyses HMWHA. We further report a correlation between the levels of HYAL2 secretion by human blastocysts, morphological scores, and implantation potential. Taken together, the data suggest a pivotal role for uNK cells in embryo biosensing and endometrial fate decisions at implantation.<\/jats:p>","DOI":"10.1096\/fj.202002217r","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T07:31:58Z","timestamp":1616398318000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Embryo biosensing by uterine natural killer cells determines endometrial fate decisions at implantation"],"prefix":"10.1096","volume":"35","author":[{"given":"Chow\u2010Seng","family":"Kong","sequence":"first","affiliation":[{"name":"Centre for Early Life, Warwick Medical School University of Warwick Coventry UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra Almansa","family":"Ordo\u00f1ez","sequence":"additional","affiliation":[{"name":"Eugin Clinica Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Turner","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Medicine University Hospitals Coventry and Warwickshire NHS Trust Coventry UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Tremaine","sequence":"additional","affiliation":[{"name":"Comparative Biomedical Sciences, The Royal Veterinary College University of London Hatfield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Muter","sequence":"additional","affiliation":[{"name":"Centre for Early Life, Warwick Medical School University of Warwick Coventry UK"},{"name":"Tommy\u2019s National Centre for Miscarriage Research University Hospitals Coventry &amp; Warwickshire NHS Trust Coventry UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma S.","family":"Lucas","sequence":"additional","affiliation":[{"name":"Centre for Early Life, Warwick Medical School University of Warwick Coventry UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Salisbury","sequence":"additional","affiliation":[{"name":"Centre for Early Life, Warwick Medical School University of Warwick Coventry UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Vassena","sequence":"additional","affiliation":[{"name":"Eugin Clinica Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Tiscornia","sequence":"additional","affiliation":[{"name":"Eugin Clinica Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali A.","family":"Fouladi\u2010Nashta","sequence":"additional","affiliation":[{"name":"Comparative Biomedical Sciences, The Royal Veterinary College University of London Hatfield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraldine","family":"Hartshorne","sequence":"additional","affiliation":[{"name":"Centre for Early Life, Warwick Medical School University of Warwick Coventry UK"},{"name":"Centre for Reproductive Medicine University Hospitals Coventry and Warwickshire NHS Trust Coventry UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan J.","family":"Brosens","sequence":"additional","affiliation":[{"name":"Centre for Early Life, Warwick Medical School University of Warwick Coventry UK"},{"name":"Tommy\u2019s National Centre for Miscarriage Research University Hospitals Coventry &amp; Warwickshire NHS Trust Coventry UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6908-3794","authenticated-orcid":false,"given":"Paul J.","family":"Brighton","sequence":"additional","affiliation":[{"name":"Centre for Early Life, Warwick Medical School University of Warwick Coventry UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2014-1045"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/418300"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-017-1107-z"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041424"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-100003"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2005594"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0899"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.31274"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05938.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052252"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.140.10.7070"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-149153"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2017-03064"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010258"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-0763-1"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1511-7"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00031.2019"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.13837"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2019.04.040"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deaa149"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep03894"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.114.122846"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-1309"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14777"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-16-0240"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hoz033"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2013.12.009"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.2028"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21031036"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2013.05.009"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(00)00518-5"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1177\/33.10.4045184"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.22.13997"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cww089"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2005.12.033"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwn006"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2008.07.006"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.100594.109"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1089\/107999004323065093"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2007.09.002"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2006.05.009"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvh069"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M805144200"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/ppe.12613"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(02)04694-0"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198807283190401"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)58144-8"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2017.04.001"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005601"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.262774.120"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811841106"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000046"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812722106"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmt025"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep08689"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.13448"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2013.07.1996"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2222"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gat032"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.theriogenology.2016.03.017"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004410100452"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-0436.1992.tb00500.x"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.402347"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-018-0605-5"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202002217R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202002217R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202002217R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:18:35Z","timestamp":1761671915000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202002217R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,22]]},"references-count":64,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1096\/fj.202002217R"],"URL":"https:\/\/doi.org\/10.1096\/fj.202002217r","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.739801585.793584095","asserted-by":"object"}]},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,22]]},"assertion":[{"value":"2020-10-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e21336"}}