{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:26:54Z","timestamp":1745468814719,"version":"3.40.4"},"reference-count":29,"publisher":"S. Karger AG","issue":"1-6","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sex Dev"],"published-print":{"date-parts":[[2020]]},"abstract":"SOX17 activity in the uterine epithelium is essential for the implantation of mouse embryos. Previously, we demonstrated that female <i>Sox17<\/i> heterozygous mutant mice are subfertile, and 2 active copies of <i>Sox17<\/i> are required for the proper implantation of mouse embryos. To understand which implantation step is most sensitive to the <i>Sox17<\/i> gene dosage, we comprehensively investigated the phenotypes and RNA transcriptomes of <i>Sox17<\/i> heterozygous mutant mice. Uterine <i>Sox17<\/i> expression drastically changed according to estrous cycle and during early pregnancy. The highest <i>Sox17<\/i> expression was observed during the receptive period for blastocyst implantation. <i>Sox17<\/i> heterozygous uterine epithelia showed ectopic high-level expression of SOX9, another SOX factor that is normally expressed in the uterine gland. Three-dimensional analysis of the uterus on day 5 of pregnancy revealed no crypt formation near the healthy blastocysts in the <i>Sox17<\/i> heterozygous uterine epithelium, suggesting that early defects in embryo homing had occurred. Global transcriptional analysis revealed that the expression of Amphiregulin (<i>Areg<\/i>), a gene encoding a heparin-binding epidermal growth factor receptor ligand, was decreased drastically in <i>Sox17<\/i><sup>+\/\u2212<\/sup> uterine epithelia. These data imply that full <i>Sox17<\/i> activity is required to promote early crypt formation through proper regulation of SOX9 and AREG expression at the implantation site. <\/jats:p>","DOI":"10.1159\/000513386","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T21:06:12Z","timestamp":1617051972000},"page":"40-50","source":"Crossref","is-referenced-by-count":0,"title":["Early Crypt Formation Defects in the Uterine Epithelia of <b><i>Sox17<\/i><\/b> Heterozygous Mice"],"prefix":"10.1159","volume":"14","author":[{"given":"Yoshikazu","family":"Hirate","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kana","family":"Hayakawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiori","family":"Kumazawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kento","family":"Miura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiakira","family":"Kanai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masami","family":"Kanai-Azuma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-018-0414-2"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2009.10.017"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.06.027"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1265"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1210\/mend.9.6.8592515"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1071\/bi9770289"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2016.05.006"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1242\/dev.147512"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1038\/srep24171"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn923"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.06.011"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-51751-3"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22046"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2016.07.021"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2467"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.3791\/4389"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.3.1047"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1210\/me.2011-1355"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1292\/jvms1939.44.125"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1210\/mend.14.8.0498"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1038\/359076a0"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2015.085"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1242\/dev.086702"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/den501"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06652-w"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds241"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03092-4"}],"container-title":["Sexual Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/513386","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/513386","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:14:04Z","timestamp":1745424844000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000513386"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020]]},"references-count":29,"journal-issue":{"issue":"1-6","published-online":{"date-parts":[[2021,7,30]]},"published-print":{"date-parts":[[2021,9,10]]}},"URL":"https:\/\/doi.org\/10.1159\/000513386","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.14184788","asserted-by":"subject"}]},"ISSN":["1661-5425","1661-5433"],"issn-type":[{"type":"print","value":"1661-5425"},{"type":"electronic","value":"1661-5433"}],"subject":[],"published":{"date-parts":[[2020]]}}}