{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T09:47:03Z","timestamp":1778924823850,"version":"3.51.4"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI 19H03144"],"award-info":[{"award-number":["KAKENHI 19H03144"]}],"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":["KAKENHI 19H03796"],"award-info":[{"award-number":["KAKENHI 19H03796"]}],"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":["KAKENHI 19K16022"],"award-info":[{"award-number":["KAKENHI 19K16022"]}],"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":["KAKENHI 21J00509"],"award-info":[{"award-number":["KAKENHI 21J00509"]}],"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":"crossref","award":["KAKENHI 21K16763"],"award-info":[{"award-number":["KAKENHI 21K16763"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["FORCE 21gm4010010h0002"],"award-info":[{"award-number":["FORCE 21gm4010010h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["WISE 21gk0210021h0003"],"award-info":[{"award-number":["WISE 21gk0210021h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["BIRTHDAY 21gk0110056h0001"],"award-info":[{"award-number":["BIRTHDAY 21gk0110056h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018504","name":"NIPRO","doi-asserted-by":"crossref","award":["joint research funding"],"award-info":[{"award-number":["joint research funding"]}],"id":[{"id":"10.13039\/100018504","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Reprod. Sci."],"published-print":{"date-parts":[[2022,5]]},"DOI":"10.1007\/s43032-021-00816-8","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T21:02:27Z","timestamp":1638478947000},"page":"1457-1462","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Uterine Receptivity is Reflected by LIF Expression in the Cervix"],"prefix":"10.1007","volume":"29","author":[{"given":"Yamato","family":"Fukui","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0241-9780","authenticated-orcid":false,"given":"Yasushi","family":"Hirota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shizu","family":"Aikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chihiro","family":"Ishizawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rei","family":"Iida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuaki","family":"Kaku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyuki","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun","family":"Akaeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takehiro","family":"Hiraoka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsunori","family":"Matsuo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Osuga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"816_CR1","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1093\/humupd\/dmv016","volume":"21","author":"MC Inhorn","year":"2015","unstructured":"Inhorn MC, Patrizio P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015;21:411\u201326.","journal-title":"Hum Reprod Update"},{"key":"816_CR2","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/rmb2.12358","volume":"20","author":"O Ishihara","year":"2021","unstructured":"Ishihara O, Jwa SC, Kuwahara A, Katagiri Y, Kuwabara Y, Hamatani T, Harada M, Osuga Y. Assisted reproductive technology in Japan: a summary report for 2018 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology. Reprod Med Biol. 2021;20:3\u201312.","journal-title":"Reprod Med Biol"},{"key":"816_CR3","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1038\/nm.3012","volume":"18","author":"J Cha","year":"2012","unstructured":"Cha J, Sun X, Dey SK. Mechanisms of implantation: strategies for successful pregnancy. Nat Med. 2012;18:1754\u201367.","journal-title":"Nat Med"},{"key":"816_CR4","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/s12522-013-0153-1","volume":"12","author":"M Egashira","year":"2013","unstructured":"Egashira M, Hirota Y. Uterine receptivity and embryo-uterine interactions in embryo implantation: lessons from mice. Reprod Med Biol. 2013;12:127\u201332.","journal-title":"Reprod Med Biol"},{"key":"816_CR5","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1002\/rmb2.12280","volume":"18","author":"Y Fukui","year":"2019","unstructured":"Fukui Y, Hirota Y, Matsuo M, Gebril M, Akaeda S, Hiraoka T, Osuga Y. Uterine receptivity, embryo attachment, and embryo invasion: multistep processes in embryo implantation. Reprod Med Biol. 2019;18:234\u201340.","journal-title":"Reprod Med Biol"},{"key":"816_CR6","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1507\/endocrj.EJ18-0431","volume":"66","author":"Y Hirota","year":"2019","unstructured":"Hirota Y. Progesterone governs endometrial proliferation-differentiation switching and blastocyst implantation. Endocr J. 2019;66:199\u2013206.","journal-title":"Endocr J"},{"key":"816_CR7","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1210\/me.2014-1097","volume":"28","author":"H Haraguchi","year":"2014","unstructured":"Haraguchi H, Saito-Fujita T, Hirota Y, Egashira M, Matsumoto L, Matsuo M, Hiraoka T, Koga K, Yamauchi N, Fukayama M, Bartos A, Cha J, Dey SK, Fujii T, Osuga Y. MicroRNA-200a locally attenuates progesterone signaling in the cervix, preventing embryo implantation. Mol Endocrinol. 2014;28:1108\u201317.","journal-title":"Mol Endocrinol"},{"key":"816_CR8","doi-asserted-by":"publisher","first-page":"e50927","DOI":"10.15252\/embr.202050927","volume":"22","author":"S Akaeda","year":"2021","unstructured":"Akaeda S, Hirota Y, Fukui Y, Aikawa S, Shimizu-Hirota R, Kaku T, Gebril M, Hirata T, Hiraoka T, Matsuo M, Haraguchi H, Saito-Kanatani M, Takeda N, Fujii T, Osuga Y. Retinoblastoma protein promotes uterine epithelial cell cycle arrest and necroptosis for embryo invasion. EMBO Rep. 2021;22:e50927.","journal-title":"EMBO Rep"},{"key":"816_CR9","doi-asserted-by":"publisher","first-page":"15523","DOI":"10.1038\/s41598-020-72640-0","volume":"10","author":"T Hiraoka","year":"2020","unstructured":"Hiraoka T, Hirota Y, Fukui Y, Gebril M, Kaku T, Aikawa S, Hirata T, Akaeda S, Matsuo M, Haraguchi H, Saito-Kanatani M, Shimizu-Hirota R, Takeda N, Yoshino O, Fujii T, Osuga Y. Differential roles of uterine epithelial and stromal STAT3 coordinate uterine receptivity and embryo attachment. Sci Rep. 2020;10:15523.","journal-title":"Sci Rep"},{"key":"816_CR10","doi-asserted-by":"publisher","first-page":"bqaa195","DOI":"10.1210\/endocr\/bqaa195","volume":"161","author":"M Gebril","year":"2020","unstructured":"Gebril M, Hirota Y, Aikawa S, Fukui Y, Kaku T, Matsuo M, Hirata T, Akaeda S, Hiraoka T, Shimizu-Hirota R, Takeda N, Taha T, Balah OA, Elnoury MAH, Fujii T, Osuga Y. Uterine epithelial progesterone receptor governs uterine receptivity through epithelial cell differentiation. Endocrinology. 2020;161:bqaa195.","journal-title":"Endocrinology"},{"key":"816_CR11","doi-asserted-by":"publisher","first-page":"3186","DOI":"10.1172\/JCI98931","volume":"128","author":"L Matsumoto","year":"2018","unstructured":"Matsumoto L, Hirota Y, Saito-Fujita T, Takeda N, Tanaka T, Hiraoka T, Akaeda S, Fujita H, Shimizu-Hirota R, Igaue S, Matsuo M, Haraguchi H, Saito-Kanatani M, Fujii T, Osuga Y. HIF2alpha in the uterine stroma permits embryo invasion and luminal epithelium detachment. J Clin Invest. 2018;128:3186\u201397.","journal-title":"J Clin Invest"},{"key":"816_CR12","doi-asserted-by":"publisher","first-page":"bqab169","DOI":"10.1210\/endocr\/bqab169","volume":"162","author":"Y Fukui","year":"2021","unstructured":"Fukui Y, Hirota Y, Saito-Fujita T, Aikawa S, Hiraoka T, Kaku T, Hirata T, Akaeda S, Matsuo M, Shimizu-Hirota R, Takeda N, Ikawa M, Osuga Y. Uterine epithelial LIF receptors contribute to implantation chamber formation in blastocyst attachment. Endocrinology. 2021;162:bqab169.","journal-title":"Endocrinology"},{"key":"816_CR13","doi-asserted-by":"publisher","first-page":"bqz005","DOI":"10.1210\/endocr\/bqz005","volume":"161","author":"M Matsuo","year":"2020","unstructured":"Matsuo M, Hirota Y, Fukui Y, Fujita H, Saito-Fujita T, Kaku T, Gebril M, Hirata T, Akaeda S, Hiraoka T, Tanaka T, Haraguchi H, Saito-Kanatani M, Shimizu-Hirota R, Takeda N, Fujii T, Osuga Y. Levonorgestrel inhibits embryo attachment by eliminating uterine induction of leukemia inhibitory factor. Endocrinology. 2020;161:bqz005.","journal-title":"Endocrinology."},{"key":"816_CR14","doi-asserted-by":"publisher","first-page":"4365","DOI":"10.1210\/endo.141.12.7855","volume":"141","author":"JR Chen","year":"2000","unstructured":"Chen JR, Cheng JG, Shatzer T, Sewell L, Hernandez L, Stewart CL. Leukemia inhibitory factor can substitute for nidatory estrogen and is essential to inducing a receptive uterus for implantation but is not essential for subsequent embryogenesis. Endocrinology. 2000;141:4365\u201372.","journal-title":"Endocrinology"},{"key":"816_CR15","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1210\/mend.14.8.0498","volume":"14","author":"H Song","year":"2000","unstructured":"Song H, Lim H, Das SK, Paria BC, Dey SK. Dysregulation of EGF family of growth factors and COX-2 in the uterus during the preattachment and attachment reactions of the blastocyst with the luminal epithelium correlates with implantation failure in LIF-deficient mice. Mol Endocrinol. 2000;14:1147\u201361.","journal-title":"Mol Endocrinol"},{"key":"816_CR16","doi-asserted-by":"publisher","first-page":"8680","DOI":"10.1073\/pnas.151180898","volume":"98","author":"JG Cheng","year":"2001","unstructured":"Cheng JG, Chen JR, Hernandez L, Alvord WG, Stewart CL. Dual control of LIF expression and LIF receptor function regulate Stat3 activation at the onset of uterine receptivity and embryo implantation. Proc Natl Acad Sci U S A. 2001;98:8680\u20135.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"816_CR17","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/359076a0","volume":"359","author":"CL Stewart","year":"1992","unstructured":"Stewart CL, Kaspar P, Brunet LJ, Bhatt H, Gadi I, Kontgen F, Abbondanzo SJ. Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Nature. 1992;359:76\u20139.","journal-title":"Nature"},{"key":"816_CR18","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1210\/me.2013-1086","volume":"27","author":"X Sun","year":"2013","unstructured":"Sun X, Bartos A, Whitsett JA, Dey SK. Uterine deletion of Gp130 or Stat3 shows implantation failure with increased estrogenic responses. Mol Endocrinol. 2013;27:1492\u2013501.","journal-title":"Mol Endocrinol"},{"key":"816_CR19","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1002\/mrd.22118","volume":"80","author":"S Zhang","year":"2013","unstructured":"Zhang S, Kong S, Lu J, Wang Q, Chen Y, Wang W, Wang B, Wang H. Deciphering the molecular basis of uterine receptivity. Mol Reprod Dev. 2013;80:8\u201321.","journal-title":"Mol Reprod Dev"},{"key":"816_CR20","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1016\/j.fertnstert.2013.05.004","volume":"100","author":"M Ruiz-Alonso","year":"2013","unstructured":"Ruiz-Alonso M, Blesa D, D\u00edaz-Gimeno P, G\u00f3mez E, Fern\u00e1ndez-S\u00e1nchez M, Carranza F, Carrera J, Vilella F, Pellicer A, Sim\u00f3n C. The endometrial receptivity array for diagnosis and personalized embryo transfer as a treatment for patients with repeated implantation failure. Fertil Steril. 2013;100:818\u201324.","journal-title":"Fertil Steril"},{"key":"816_CR21","doi-asserted-by":"publisher","first-page":"15577","DOI":"10.1073\/pnas.1009324107","volume":"107","author":"Y Hirota","year":"2010","unstructured":"Hirota Y, Acar N, Tranguch S, Burnum KE, Xie H, Kodama A, Osuga Y, Ustunel I, Friedman DB, Caprioli RM, Daikoku T, Dey SK. Uterine FK506-binding protein 52 (FKBP52)-peroxiredoxin-6 (PRDX6) signaling protects pregnancy from overt oxidative stress. Proc Natl Acad Sci U S A. 2010;107:15577\u201382.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"816_CR22","doi-asserted-by":"publisher","first-page":"557184","DOI":"10.3389\/fimmu.2020.557184","volume":"11","author":"Y Ono","year":"2020","unstructured":"Ono Y, Yoshino O, Hiraoka T, Sato E, Fukui Y, Ushijima A, Nawaz A, Hirota Y, Wada S, Tobe K, Nakashima A, Osuga Y, Saito S. CD206+ M2-like macrophages are essential for successful implantation. Front Immunol. 2020;11:557184.","journal-title":"Front Immunol"},{"key":"816_CR23","first-page":"691","volume":"9","author":"SK Das","year":"1995","unstructured":"Das SK, Chakraborty I, Paria BC, Wang XN, Plowman G, Dey SK. Amphiregulin is an implantation-specific and progesterone-regulated gene in the mouse uterus. Mol Endocrinol. 1995;9:691\u2013705.","journal-title":"Mol Endocrinol"},{"key":"816_CR24","doi-asserted-by":"publisher","first-page":"e93","DOI":"10.1016\/j.fertnstert.2019.08.079","volume":"112","author":"RW Noyes","year":"2019","unstructured":"Noyes RW, Hertig AT, Rock J. Reprint of: Dating the endometrial biopsy. Fertil Steril. 2019;112:e93\u2013115.","journal-title":"Fertil Steril"},{"issue":"Suppl 2","key":"816_CR25","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1093\/humrep\/10.suppl_2.140","volume":"10","author":"A Psychoyos","year":"1995","unstructured":"Psychoyos A, Nikas G, Sarantis L, Gravanis A. Hormonal anti-implantation agents: antiprogestins. Hum Reprod. 1995;10(Suppl 2):140\u201350.","journal-title":"Hum Reprod"},{"key":"816_CR26","first-page":"101","volume":"6","author":"MT McMaster","year":"1992","unstructured":"McMaster MT, Teng CT, Dey SK, Andrews GK. Lactoferrin in the mouse uterus: analyses of the preimplantation period and regulation by ovarian steroids. Mol Endocrinol. 1992;6:101\u201311.","journal-title":"Mol Endocrinol"},{"key":"816_CR27","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1677\/jme.0.0290239","volume":"29","author":"S Heikaus","year":"2002","unstructured":"Heikaus S, Winterhager E, Traub O, Gr\u00fcmmer R. Responsiveness of endometrial genes Connexin26, Connexin 43, C3 and clusterin to primary estrogen, selective estrogen receptor modulators, phyto- and xenoestrogens. J Mol Endocrinol. 2002;29:239\u201349.","journal-title":"J Mol Endocrinol"},{"key":"816_CR28","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1006\/dbio.2002.0645","volume":"245","author":"H Matsumoto","year":"2002","unstructured":"Matsumoto H, Zhao X, Das SK, Hogan BL, Dey SK. Indian hedgehog as a progesterone-responsive factor mediating epithelial-mesenchymal interactions in the mouse uterus. Dev Biol. 2002;245:280\u201390.","journal-title":"Dev Biol"}],"container-title":["Reproductive Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43032-021-00816-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43032-021-00816-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43032-021-00816-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:17:40Z","timestamp":1649859460000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43032-021-00816-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,2]]},"references-count":28,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["816"],"URL":"https:\/\/doi.org\/10.1007\/s43032-021-00816-8","relation":{},"ISSN":["1933-7191","1933-7205"],"issn-type":[{"value":"1933-7191","type":"print"},{"value":"1933-7205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,2]]},"assertion":[{"value":"12 October 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The experimental procedures for mice were approved by the Animal Experiment Committee of The University of Tokyo (Approval nos.: P16-066). The study using human uterine specimens was approved by the Ethics Committee of The University of Tokyo (Registration no.: 0324). Uterine samples were collected in this study, for which participants gave signed informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}