{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:22:41Z","timestamp":1790680961747,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T00:00:00Z","timestamp":1600732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19H03801"],"award-info":[{"award-number":["19H03801"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K19624"],"award-info":[{"award-number":["18K19624"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18H06258"],"award-info":[{"award-number":["18H06258"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pregnancy rate of women decreases with age due to declining quality of oocytes and embryos. However, there is no established method to improve pregnancy rate in aging women. In this study, we identified a senescence\u2010associated secretory phenotype (SASP) factor partially responsible for the decline in embryo implantation potential. Based on microarray analysis using young and aging human embryos at the same morphological grade, 702 genes showed &gt;fivefold increases in aging human blastocysts. Among these genes, C\u2010X\u2010C motif chemokine 5 (<jats:italic>CXCL5<\/jats:italic>) showed 7.7\u2010fold increases in aging human blastocysts. However, no\u2010age\u2010dependent changes in expression of the CXCR2, the cognate receptor for CXCL5, were found. In aging mice, <jats:italic>Cxcl5<\/jats:italic> transcript levels were also increased in oocytes and embryos. Treatment of young mouse embryos with CXCL5 decreased implantation rates, together with increased expression of aging markers (<jats:italic>P53<\/jats:italic>, <jats:italic>P21<\/jats:italic>, <jats:italic>Pai<\/jats:italic>\u2010<jats:italic>1<\/jats:italic>, and <jats:italic>Il<\/jats:italic>\u2010<jats:italic>6<\/jats:italic>). Moreover, CXCL5 treatment suppressed trophoblast outgrowth in young mouse blastocysts. Conversely, suppression of CXCL5\u2010CXCR2 signaling in aging mouse embryos using neutralizing antibodies and a receptor antagonist improved the implantation rate, leading to increases in pregnancy and delivery of normal pups. The gene expression pattern of these embryos was comparable to that in young mouse embryos showing enriched cell proliferation\u2010related pathways. In conclusion, we identified CXCL5 as a SASP factor in human and mouse embryos and suppression of CXCL5\u2010CXCR2 signaling during embryo culture improved pregnancy success in aging mice. Future analysis on CXCL5\u2010CXCR2 signaling suppression in human embryos could be the basis to improve embryo development and pregnancy outcome in middle\u2010aged infertile patients.<\/jats:p>","DOI":"10.1111\/acel.13240","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T11:52:39Z","timestamp":1600775559000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["CXCL5\u2010CXCR2 signaling is a senescence\u2010associated secretory phenotype in preimplantation embryos"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0641-1244","authenticated-orcid":false,"given":"Yuta","family":"Kawagoe","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Advanced Reproduction Research Center International University of Health and Welfare School of Medicine Narita Japan"},{"name":"The United Graduate School of Agriculture Sciences Iwate University Morioka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikko","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Institute of Advanced BioMedical Engineering and Science Tokyo Women's Medical University Shinjuku\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yorino","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Advanced Reproduction Research Center International University of Health and Welfare School of Medicine Narita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Advanced Reproduction Research Center International University of Health and Welfare School of Medicine Narita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuei","family":"Matsubara","sequence":"additional","affiliation":[{"name":"The United Graduate School of Agriculture Sciences Iwate University Morioka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Advanced Reproduction Research Center International University of Health and Welfare School of Medicine Narita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2784"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.03.038"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI3145"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0260OC"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.10.050"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2008.05.012"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806883105"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(01)02151-1"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2009.00534.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00327"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.11.002"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-121808-102144"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0060301"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.11.012"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2013.11.004"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2010.03.003"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(00)00518-5"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101885"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/gly290"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-7-r75"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041610321"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deq014"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh241"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64164-8"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-09-0341"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-0213"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4755-11-37"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1448"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.03.039"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22445"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2218499"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00438.x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)93060-M"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1909"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871528111312050003"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.5239"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28819"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)91205-M"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(99)00229-4"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00049.2003"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.17.10095"},{"issue":"3","key":"e_1_2_9_43_1","first-page":"e137","article-title":"Regulation of trophoblast invasion: The role of matrix metalloproteinases","volume":"5","author":"Zhu J. Y.","year":"2012","journal-title":"Reviews in Obstetrics Gynecology"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0000000000000065"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13240","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.13240","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13240","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T23:34:16Z","timestamp":1693870456000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.13240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,22]]},"references-count":43,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1111\/acel.13240"],"URL":"https:\/\/doi.org\/10.1111\/acel.13240","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,22]]},"assertion":[{"value":"2020-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13240"}}