{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:03:21Z","timestamp":1792785801695,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T00:00:00Z","timestamp":1564099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["20720180039"],"award-info":[{"award-number":["20720180039"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81601285"],"award-info":[{"award-number":["81601285"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81490744"],"award-info":[{"award-number":["81490744"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81830045"],"award-info":[{"award-number":["81830045"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key R&D program of China","award":["2018YFC1004404"],"award-info":[{"award-number":["2018YFC1004404"]}]},{"name":"National Key R&D program of China","award":["2017YFC1001402"],"award-info":[{"award-number":["2017YFC1001402"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dingkun Pill (DK) is one of the representative traditional Chinese medicines, which has been used in the treatment of gynecological diseases for hundreds of years. Accumulative observations and evidence have shown the beneficial effects of DK, including enhancing the function of hypothalamic-pituitary-ovarian axis. However, the underlying mechanisms remain elusive. In this study, the effects of DK on uterine receptivity and implantation were explored by a series of studies with different mouse models. The results showed that DK can advance the time of implantation by influencing the expression of estrogen target genes to facilitate embryo implantation. DK was efficient to activate embryo implantation at the presence of suboptimal estrogen in delayed implantation mouse model. Our further study revealed that the improvement of DK on receptivity establishment is attributed to the differential regulation of DK on implantation-associated genes. This study provides previously unappreciated molecular mechanism of DK in embryo implantation and benefits the potential clinical application of DK in human reproduction improvement.<\/jats:p>","DOI":"10.1093\/biolre\/ioz141","type":"journal-article","created":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T05:20:25Z","timestamp":1564118425000},"page":"695-703","source":"Crossref","is-referenced-by-count":11,"title":["Traditional Chinese medicine Dingkun Pill facilitates uterine receptivity for implantation in mice\u2020"],"prefix":"10.1093","volume":"101","author":[{"given":"Lin","family":"Huang","sequence":"first","affiliation":[{"name":"Reproductive Medical Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People\u2019s Republic of China"},{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen, Fujian, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lemeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People\u2019s Republic of China"},{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen, Fujian, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haili","family":"Bao","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People\u2019s Republic of China"},{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen, Fujian, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchun","family":"Xu","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People\u2019s Republic of China"},{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen, Fujian, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiqing","family":"Meng","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People\u2019s Republic of China"},{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen, Fujian, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manting","family":"Qiao","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People\u2019s Republic of China"},{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen, Fujian, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibin","family":"Wang","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People\u2019s Republic of China"},{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen, Fujian, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangbo","family":"Kong","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People\u2019s Republic of China"},{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen, Fujian, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,26]]},"reference":[{"key":"2019112123502026000_ref1","first-page":"805","article-title":"The research of estrogen receptor modulator and correlative Chinese herbs","volume":"27","author":"He","year":"2002","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"2019112123502026000_ref2","doi-asserted-by":"crossref","first-page":"178","DOI":"10.4103\/2096-2924.248482","article-title":"Modern clinical application of ding 1541","volume":"2","author":"Huang","year":"2018","journal-title":"Reprod Dev Med"},{"key":"2019112123502026000_ref3","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/S0140-6736(06)68117-8","article-title":"Psychosocial burden of infertility and assisted reproduction","volume":"367","author":"Schmidt","year":"2006","journal-title":"Lancet"},{"key":"2019112123502026000_ref4","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s12958-018-0414-2","article-title":"Recurrent implantation failure-update overview on etiology, diagnosis, treatment and future directions","volume":"16","author":"Bashiri","year":"2018","journal-title":"Reprod Biol Endocrinol"},{"key":"2019112123502026000_ref5","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S1521-6934(02)00130-X","article-title":"The endometrium as a cause of implantation failure","volume":"17","author":"Sharkey","year":"2003","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"2019112123502026000_ref6","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/435034a","article-title":"Reproductive biology: Fatty link to fertility","volume":"435","author":"Dey","year":"2005","journal-title":"Nature"},{"key":"2019112123502026000_ref7","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1172\/JCI92862","article-title":"Polycomb subunit BMI1 determines uterine progesterone responsiveness essential for normal embryo implantation","volume":"128","author":"Xin","year":"2018","journal-title":"J Clin Invest"},{"key":"2019112123502026000_ref8","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/j.1749-6632.1986.tb20920.x","article-title":"Uterine receptivity for nidation","volume":"476","author":"Psychoyos","year":"1986","journal-title":"Ann N Y Acad Sci"},{"key":"2019112123502026000_ref9","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1242\/dev.120.5.1071","article-title":"Heparin-binding Egf-like growth-factor gene is induced in the mouse uterus temporally by the blastocyst solely at the site of its apposition\u2014a possible ligand for interaction with blastocyst Egf-receptor in implantation","volume":"120","author":"Das","year":"1994","journal-title":"Dev"},{"key":"2019112123502026000_ref10","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/(SICI)1098-2795(199610)45:2<183::AID-MRD11>3.0.CO;2-2","article-title":"The uterus is a potential site for anandamide synthesis and hydrolysis: differential profiles of anandamide synthase and hydrolase activities in the mouse uterus during the periimplantation period","volume":"45","author":"Paria","year":"1996","journal-title":"Mol Reprod Dev"},{"key":"2019112123502026000_ref11","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1006\/dbio.2000.9767","article-title":"Embryo implantation","volume":"223","author":"Carson","year":"2000","journal-title":"Dev Biol"},{"key":"2019112123502026000_ref12","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1095\/biolreprod55.5.1098","article-title":"Spatial and temporal analyses of integrin and Muc-1 expression in porcine uterine epithelium and trophectoderm in vivo","volume":"55","author":"Bowen","year":"1996","journal-title":"Biol Reprod"},{"key":"2019112123502026000_ref13","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1210\/endo.136.8.7628404","article-title":"Expression and steroid hormonal-control of Muc-1 in the mouse uterus","volume":"136","author":"Surveyor","year":"1995","journal-title":"Endocrinol"},{"key":"2019112123502026000_ref14","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/s41467-018-03092-4","article-title":"Tridimensional visualization reveals direct communication between the embryo and glands critical for implantation","volume":"9","author":"Yuan","year":"2018","journal-title":"Nat Commun"},{"key":"2019112123502026000_ref15","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.yexcr.2008.07.025","article-title":"HB-EGF: a unique mediator of embryo-uterine interactions during implantation","volume":"315","author":"Lim","year":"2009","journal-title":"Exp Cell Res"},{"key":"2019112123502026000_ref16","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1016\/j.devcel.2011.09.010","article-title":"Conditional deletion of Msx homeobox genes in the uterus inhibits blastocyst implantation by altering uterine receptivity","volume":"21","author":"Daikoku","year":"2011","journal-title":"Dev Cell"},{"key":"2019112123502026000_ref17","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1210\/en.2003-1361","article-title":"Cochlin, a secreted von Willebrand factor type a domain-containing factor, is regulated by leukemia inhibitory factor in the uterus at the time of embryo implantation","volume":"145","author":"Rodriguez","year":"2004","journal-title":"Endocrinol"},{"key":"2019112123502026000_ref18","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.1073\/pnas.0530162100","article-title":"Estrogen is a critical determinant that specifies the duration of the window of uterine receptivity for implantation","volume":"100","author":"Ma","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2019112123502026000_ref19","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0092-8674(00)80402-X","article-title":"Multiple female reproductive failures in cyclooxygenase 2-deficient mice","volume":"91","author":"Lim","year":"1997","journal-title":"Cell"},{"key":"2019112123502026000_ref20","doi-asserted-by":"crossref","first-page":"5653","DOI":"10.1016\/j.febslet.2006.09.014","article-title":"Profiling of E-cadherin, beta-catenin and Ca(2+) in embryo-uterine interactions at implantation","volume":"580","author":"Jha","year":"2006","journal-title":"FEBS Lett"},{"key":"2019112123502026000_ref21","doi-asserted-by":"crossref","first-page":"9960","DOI":"10.1073\/pnas.0501632102","article-title":"Variation in commercial rodent diets induces disparate molecular and physiological changes in the mouse uterus","volume":"102","author":"Wang","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2019112123502026000_ref22","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1055\/s-2007-991037","article-title":"Physiology and pathology of implantation in the human and nonhuman primate","volume":"25","author":"Fazleabas","year":"2007","journal-title":"Semin Reprod Med"},{"key":"2019112123502026000_ref23","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1093\/humupd\/4.5.465","article-title":"Molecular control of the implantation window","volume":"4","author":"Tabibzadeh","year":"1998","journal-title":"Hum Reprod Update"},{"key":"2019112123502026000_ref24","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1056\/NEJM199906103402304","article-title":"Time of implantation of the conceptus and loss of pregnancy","volume":"340","author":"Wilcox","year":"1999","journal-title":"N Engl J Med"},{"key":"2019112123502026000_ref25","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1093\/humrep\/der009","article-title":"The association of maternal factors with delayed implantation and the initial rise of urinary human chorionic gonadotrophin","volume":"26","author":"Jukic","year":"2011","journal-title":"Hum Reprod"},{"key":"2019112123502026000_ref26","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.rbmo.2013.06.010","article-title":"Oestrogen and progesterone action on endometrium: a translational approach to understanding endometrial receptivity","volume":"27","author":"Young","year":"2013","journal-title":"Reprod Biomed Online"},{"key":"2019112123502026000_ref27","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1093\/humupd\/dml033","article-title":"The human endometrium as a fertility-determining factor","volume":"12","author":"Strowitzki","year":"2006","journal-title":"Hum Reprod Update"},{"key":"2019112123502026000_ref28","first-page":"124","article-title":"Extraction study of eighteen sex hormones from antler velvet","volume":"32","author":"Chun-yan","year":"2016","journal-title":"J Mol Sci"},{"key":"2019112123502026000_ref29","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.jep.2005.01.033","article-title":"In vitro estrogenic activities of Chinese medicinal plants traditionally used for the management of menopausal symptoms","volume":"98","author":"Zhang","year":"2005","journal-title":"J Ethnopharmacol"},{"key":"2019112123502026000_ref30","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1142\/S0192415X17500756","article-title":"Estrogenic potentials of traditional Chinese medicine","volume":"45","author":"Kiyama","year":"2017","journal-title":"Am J Chin Med"},{"key":"2019112123502026000_ref31","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/1477-7827-12-97","article-title":"Evidence of ERalpha and ERbeta selectivity and partial estrogen agonism in traditional Chinese medicine","volume":"12","author":"Tiosano","year":"2014","journal-title":"Reprod Biol Endocrinol"},{"key":"2019112123502026000_ref32","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1530\/ror.0.0030052","article-title":"Cytokines and implantation","volume":"3","author":"Sharkey","year":"1998","journal-title":"Rev Reprod"},{"key":"2019112123502026000_ref33","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/359076a0","article-title":"Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor","volume":"359","author":"Stewart","year":"1992","journal-title":"Nature"},{"key":"2019112123502026000_ref34","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1095\/biolreprod67.2.460","article-title":"In vivo effect of leukemia inhibitory factor (LIF) and an anti-LIF polyclonal antibody on murine embryo and fetal development following exposure at the time of transcervical blastocyst transfer","volume":"67","author":"Mitchell","year":"2002","journal-title":"Biol Reprod"},{"key":"2019112123502026000_ref35","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1677\/joe.0.1600181","article-title":"The role of leukaemia inhibitory factor in the establishment of pregnancy","volume":"160","author":"Vogiagis","year":"1999","journal-title":"J Endocrinol"},{"key":"2019112123502026000_ref36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/(SICI)1097-4652(199610)169:1<1::AID-JCP1>3.0.CO;2-S","article-title":"Estradiol induces E-cadherin degradation in mouse uterine epithelium during the estrous cycle and early pregnancy","volume":"169","author":"Potter","year":"1996","journal-title":"J Cell Physiol"},{"key":"2019112123502026000_ref37","doi-asserted-by":"crossref","first-page":"3211","DOI":"10.1093\/humrep\/13.11.3211","article-title":"Interactions between trophoblast and uterine epithelium: monitoring of adhesive forces","volume":"13","author":"Thie","year":"1998","journal-title":"Hum Reprod"}],"container-title":["Biology of Reproduction"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/biolreprod\/advance-article-pdf\/doi\/10.1093\/biolre\/ioz141\/29310121\/ioz141.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/biolreprod\/article-pdf\/101\/4\/695\/31081540\/ioz141.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/biolreprod\/article-pdf\/101\/4\/695\/31081540\/ioz141.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,24]],"date-time":"2022-09-24T13:20:48Z","timestamp":1664025648000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biolreprod\/article\/101\/4\/695\/5539043"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,26]]},"references-count":37,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,7,26]]},"published-print":{"date-parts":[[2019,10,25]]}},"URL":"https:\/\/doi.org\/10.1093\/biolre\/ioz141","relation":{},"ISSN":["0006-3363","1529-7268"],"issn-type":[{"value":"0006-3363","type":"print"},{"value":"1529-7268","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,10]]},"published":{"date-parts":[[2019,7,26]]}}}