{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T11:18:48Z","timestamp":1785583128647,"version":"3.56.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T00:00:00Z","timestamp":1312156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["rep.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Previously, we showed that heart and neural crest derivatives expressed transcript 2 (Hand2) mRNA levels dramatically increase in mouse uterine endometrial stromal cells (ESCs) as they undergo decidualization in vivo. However, to date, little is known about the expression and function of this transcription factor in mouse or human uterus decidualization. Therefore, this study was conducted to provide a more detailed assessment of Hand2 gene expression and function in the mouse uterus during the peri-implantation period and also in mouse plus human ESCs during decidualization in vitro. The results show that Hand2 mRNA and protein levels increase in the mouse uterus during decidualization and this does not depend on the presence of a conceptus. Interestingly, Hand2 mRNA and protein are present in ESCs adjacent to the luminal epithelium in the uterus prior to the onset of implantation. We find that progesterone is likely a regulator of Hand2 expression during uterine sensitization of the mouse uterus. Finally, Hand2 expression increases in mouse and human fibroblast cells as they undergo decidualization in vitro. This expression is significantly increased in response to prostaglandin E2. In particular, reduction of Hand2 expression in these cells using small hairpin RNA or small interfering RNA approaches results in the reduced extent of decidualization as shown by the reduced expression of a subset of decidualization markers. The results of this study support the hypothesis that Hand2 expression not only plays an important role in decidualization but may also play a role in obtaining proper progesterone-dependent uterine sensitization required for implantation to begin.<\/jats:p>","DOI":"10.1530\/rep-11-0060","type":"journal-article","created":{"date-parts":[[2011,4,28]],"date-time":"2011-04-28T23:08:33Z","timestamp":1304032113000},"page":"353-368","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":75,"title":["Evidence for a conserved function of heart and neural crest derivatives expressed transcript 2 in mouse and human decidualization"],"prefix":"10.1093","volume":"142","author":[{"given":"D V","family":"Huyen","sequence":"first","affiliation":[{"name":"Departments of 1Physiology 2Obstetrics and Gynecology Southern Illinois University School of Medicine, Carbondale, Illinois 62901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B M","family":"Bany","sequence":"additional","affiliation":[{"name":"Departments of 1Physiology 2Obstetrics and Gynecology Southern Illinois University School of Medicine, Carbondale, Illinois 62901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,8,1]]},"reference":[{"key":"2026010712564973700_bib1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/jez.1402660610","article-title":"Implantation and decidualization in rodents","volume":"266","author":"Abrahamsohn","year":"1993","journal-title":"Journal of Experimental Zoology"},{"key":"2026010712564973700_bib2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.ydbio.2006.03.006","article-title":"Post-implantation mouse conceptuses produce paracrine signals that regulate the uterine endometrium undergoing decidualization","volume":"294","author":"Bany","year":"2006","journal-title":"Developmental Biology"},{"key":"2026010712564973700_bib3","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/mrd.1018","article-title":"Tissue inhibitor of matrix metalloproteinase-3 expression in the mouse uterus during implantation and artificially induced decidualization","volume":"59","author":"Bany","year":"2001","journal-title":"Molecular Reproduction and Development"},{"key":"2026010712564973700_bib4","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1530\/reprod\/120.1.125","article-title":"Expression of matrix metalloproteinases 2 and 9 in the mouse uterus during implantation and oil-induced decidualization","volume":"120","author":"Bany","year":"2000","journal-title":"Journal of Reproduction and Fertility"},{"key":"2026010712564973700_bib5","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1530\/jrf.0.0610425","article-title":"Differentiation of decidual cells in mouse endometrial cell cultures","volume":"61","author":"Bell","year":"1981","journal-title":"Journal of Reproduction and Fertility"},{"key":"2026010712564973700_bib6","doi-asserted-by":"crossref","first-page":"11408","DOI":"10.1073\/pnas.88.24.11408","article-title":"Uterine expression of leukemia inhibitory factor coincides with the onset of blastocyst implantation","volume":"88","author":"Bhatt","year":"1991","journal-title":"PNAS"},{"key":"2026010712564973700_bib7","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/BF02820507","article-title":"Progesterone-dependent decidualization of the human endometrium is mediated by cAMP","volume":"6","author":"Brar","year":"1997","journal-title":"Endocrine"},{"key":"2026010712564973700_bib8","doi-asserted-by":"crossref","first-page":"3870","DOI":"10.1210\/en.2006-0167","article-title":"FOXO1A differentially regulates genes of decidualization","volume":"147","author":"Buzzio","year":"2006","journal-title":"Endocrinology"},{"key":"2026010712564973700_bib9","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1210\/en.2008-0571","article-title":"Basigin-mediated gene expression changes in mouse uterine stromal cells during implantation","volume":"150","author":"Chen","year":"2009","journal-title":"Endocrinology"},{"key":"2026010712564973700_bib10","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1530\/rep.1.00861","article-title":"Differential expression and regulation of cylooxygenases, prostaglandin E synthases and prostacyclin synthase in rat uterus during the peri-implantation period","volume":"131","author":"Cong","year":"2006","journal-title":"Reproduction"},{"key":"2026010712564973700_bib11","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/mrd.21133","article-title":"Regional development of uterine decidualization: molecular signaling by Hoxa-10","volume":"77","author":"Das","year":"2010","journal-title":"Molecular Reproduction and Development"},{"key":"2026010712564973700_bib12","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S1472-6483(10)61745-2","article-title":"Decidualization of the human endometrial stromal cell: an enigmatic transformation","volume":"7","author":"Dunn","year":"2003","journal-title":"Reproductive Biomedicine Online"},{"key":"2026010712564973700_bib13","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1210\/endo.134.1.7506205","article-title":"Prostaglandin E2 enhances human endometrial stromal cell differentiation","volume":"134","author":"Frank","year":"1994","journal-title":"Endocrinology"},{"key":"2026010712564973700_bib14","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jri.2010.03.003","article-title":"Regulation of decidualization, interleukin-11 and interleukin-15 by homeobox A 10 in endometrial stromal cells","volume":"85","author":"Godbole","year":"2010","journal-title":"Journal of Reproductive Immunology"},{"key":"2026010712564973700_bib15","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1530\/REP-07-0234","article-title":"Regulation of homeobox A10 expression in the primate endometrium by progesterone and embryonic stimuli","volume":"134","author":"Godbole","year":"2007","journal-title":"Reproduction"},{"key":"2026010712564973700_bib16","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1677\/joe.1.06451","article-title":"Forkhead transcription factor FOXO1A is critical for induction of human decidualization","volume":"189","author":"Grinius","year":"2006","journal-title":"Journal of Endocrinology"},{"key":"2026010712564973700_bib17","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1093\/molehr\/5.9.866","article-title":"Regulation of HOXA-10 and its expression in normal and abnormal endometrium","volume":"5","author":"Gui","year":"1999","journal-title":"Molecular Human Reproduction"},{"key":"2026010712564973700_bib18","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1530\/REP-07-0085","article-title":"The conceptus increases secreted phosphoprotein 1 gene expression in the mouse uterus during the progression of decidualization mainly due to its effects on uterine natural killer cells","volume":"133","author":"Herington","year":"2007","journal-title":"Reproduction"},{"key":"2026010712564973700_bib19","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1095\/biolreprod.106.056630","article-title":"Effect of the conceptus on uterine natural killer cell numbers and function in the mouse uterus during decidualization","volume":"76","author":"Herington","year":"2007","journal-title":"Biology of Reproduction"},{"key":"2026010712564973700_bib20","doi-asserted-by":"crossref","first-page":"4404","DOI":"10.1210\/en.2009-0036","article-title":"Paracrine signals from the mouse conceptus are not required for the normal progression of decidualization","volume":"150","author":"Herington","year":"2009","journal-title":"Endocrinology"},{"key":"2026010712564973700_bib21","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1530\/jrf.0.1090129","article-title":"Temporal- and hormone-dependent changes in uterine sensitization for the decidual cell reaction and decidualization in vitro of rat endometrial stromal cells","volume":"109","author":"Kennedy","year":"1997","journal-title":"Journal of Reproduction and Fertility"},{"key":"2026010712564973700_bib22","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1530\/REP-07-0328","article-title":"Prostaglandins and the initiation of blastocyst implantation and decidualization","volume":"134","author":"Kennedy","year":"2007","journal-title":"Reproduction"},{"key":"2026010712564973700_bib23","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/molehr\/gal008","article-title":"Transcription factor ETS1 is critical for human uterine decidualization","volume":"12","author":"Kessler","year":"2006","journal-title":"Molecular Human Reproduction"},{"key":"2026010712564973700_bib24","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1080\/gye.15.6.426.432","article-title":"Messenger ribonucleic acid for the mouse decidual prolactin is present and induced during in vitro decidualization of endometrial stromal cells","volume":"15","author":"Kimura","year":"2001","journal-title":"Gynecological Endocrinology"},{"key":"2026010712564973700_bib25","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1210\/en.2003-1606","article-title":"A novel immortalized human endometrial stromal cell line with normal progestational response","volume":"145","author":"Krikun","year":"2004","journal-title":"Endocrinology"},{"key":"2026010712564973700_bib26","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1038\/ng1874","article-title":"Indian hedgehog is a major mediator of progesterone signaling in the mouse uterus","volume":"38","author":"Lee","year":"2006","journal-title":"Nature Genetics"},{"key":"2026010712564973700_bib27","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1126\/science.1197454","article-title":"The antiproliferative action of progesterone in uterine epithelium is mediated by Hand2","volume":"331","author":"Li","year":"2011","journal-title":"Science"},{"key":"2026010712564973700_bib28","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1210\/mend.13.6.0284","article-title":"Hoxa-10 regulates uterine stromal cell responsiveness to progesterone during implantation and decidualization in the mouse","volume":"13","author":"Lim","year":"1999","journal-title":"Molecular Endocrinology"},{"key":"2026010712564973700_bib29","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1093\/molehr\/gan023","article-title":"Global analysis of genes regulated by HOXA10 in decidualization reveals a role in cell proliferation","volume":"14","author":"Lu","year":"2008","journal-title":"Molecular Human Reproduction"},{"key":"2026010712564973700_bib30","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1006\/dbio.1998.8907","article-title":"Abdominal B (AbdB) Hoxa genes: regulation in adult uterus by estrogen and progesterone and repression in mullerian duct by the synthetic estrogen diethylstilbestrol (DES)","volume":"197","author":"Ma","year":"1998","journal-title":"Developmental Biology"},{"key":"2026010712564973700_bib31","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1006\/dbio.2002.0645","article-title":"Indian hedgehog as a progesterone-responsive factor mediating epithelial\u2013mesenchymal interactions in the mouse uterus","volume":"245","author":"Matsumoto","year":"2002","journal-title":"Developmental Biology"},{"key":"2026010712564973700_bib32","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1530\/jrf.0.0740095","article-title":"Intraluminally injected oil induces changes in vascular permeability in the \u2018sensitized\u2019 and \u2018non-sensitized\u2019 uterus of the mouse","volume":"74","author":"Milligan","year":"1985","journal-title":"Journal of Reproduction and Fertility"},{"key":"2026010712564973700_bib33","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.placenta.2008.03.001","article-title":"Cyclooxygenase-2 derived PGE2 and PGI2 play an important role via EP2 and PPARdelta receptors in early steps of oil induced decidualization in mice","volume":"29","author":"Pakrasi","year":"2008","journal-title":"Placenta"},{"key":"2026010712564973700_bib34","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0083-6729(08)60999-1","article-title":"Hormonal control of ovoimplantation","volume":"31","author":"Psychoyos","year":"1973","journal-title":"Vitamins and Hormones"},{"key":"2026010712564973700_bib35","first-page":"17","article-title":"Hormonal control of uterine receptivity for nidation","volume":"25","author":"Psychoyos","year":"1976","journal-title":"Journal of Reproduction and Fertility Supplement"},{"key":"2026010712564973700_bib36","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":"Annals of the New York Academy of Sciences"},{"key":"2026010712564973700_bib37","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1055\/s-0029-1242989","article-title":"Endometrial decidualization: of mice and men","volume":"28","author":"Ramathal","year":"2010","journal-title":"Seminars in Reproductive Medicine"},{"issue":"Supplement A","key":"2026010712564973700_bib38","doi-asserted-by":"crossref","first-page":"S76","DOI":"10.1053\/plac.2002.0928","article-title":"Complex regulation of decidualization: a role for cytokines and proteases \u2013 a review","volume":"24","author":"Salamonsen","year":"2003","journal-title":"Placenta"},{"key":"2026010712564973700_bib39","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1186\/1471-2164-9-352","article-title":"Spatial and temporal expression of the 23 murine prolactin\/placental lactogen-related genes is not associated with their position in the locus","volume":"9","author":"Simmons","year":"2008","journal-title":"BMC Genomics"},{"key":"2026010712564973700_bib40","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1210\/mend.14.8.0498","article-title":"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","volume":"14","author":"Song","year":"2000","journal-title":"Molecular Endocrinology"},{"key":"2026010712564973700_bib41","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/ng0697-154","article-title":"Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND","volume":"16","author":"Srivastava","year":"1997","journal-title":"Nature Genetics"},{"key":"2026010712564973700_bib42","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":"2026010712564973700_bib43","doi-asserted-by":"crossref","first-page":"11613","DOI":"10.1074\/jbc.R600038200","article-title":"Prostaglandin E receptors","volume":"282","author":"Sugimoto","year":"2007","journal-title":"Journal of Biological Chemistry"},{"key":"2026010712564973700_bib44","doi-asserted-by":"crossref","first-page":"5310","DOI":"10.1210\/endo.140.11.7148","article-title":"Differential uterine expression of estrogen and progesterone receptors correlates with uterine preparation for implantation and decidualization in the mouse","volume":"140","author":"Tan","year":"1999","journal-title":"Endocrinology"},{"key":"2026010712564973700_bib45","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1172\/JCI1597","article-title":"HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium","volume":"101","author":"Taylor","year":"1998","journal-title":"Journal of Clinical Investigation"},{"key":"2026010712564973700_bib46","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1152\/physiolgenomics.00066.2003","article-title":"Activation of the protein kinase A pathway in human endometrial stromal cells reveals sequential categorical gene regulation","volume":"16","author":"Tierney","year":"2003","journal-title":"Physiological Genomics"},{"key":"2026010712564973700_bib47","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1177\/1933719108316911","article-title":"Gene expression profiling reveals putative HOXA10 downstream targets in the periimplantation mouse uterus","volume":"15","author":"Vitiello","year":"2008","journal-title":"Reproductive Sciences"},{"key":"2026010712564973700_bib48","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1471-2199-10-28","article-title":"Co-regulated expression of HAND2 and DEIN by a bidirectional promoter with asymmetrical activity in neuroblastoma","volume":"10","author":"Voth","year":"2009","journal-title":"BMC Molecular Biology"},{"key":"2026010712564973700_bib49","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.prostaglandins.2004.09.013","article-title":"Lipid signaling in embryo implantation","volume":"77","author":"Wang","year":"2005","journal-title":"Prostaglandins & Other Lipid Mediators"},{"key":"2026010712564973700_bib50","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1095\/biolreprod56.2.368","article-title":"Potential sites of prostaglandin actions in the periimplantation mouse uterus: differential expression and regulation of prostaglandin receptor genes","volume":"56","author":"Yang","year":"1997","journal-title":"Biology of Reproduction"},{"key":"2026010712564973700_bib51","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1095\/biolreprod45.1.163","article-title":"Role of cyclic adenosine 3\u2032,5\u2032-monophosphate in mediating the effect of prostaglandin E2 on decidualization in vitro","volume":"45","author":"Yee","year":"1991","journal-title":"Biology of Reproduction"},{"key":"2026010712564973700_bib52","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/0090-6980(93)90038-9","article-title":"Prostaglandin E2, cAMP and cAMP-dependent protein kinase isozymes during decidualization of rat endometrial stromal cells in vitro","volume":"46","author":"Yee","year":"1993","journal-title":"Prostaglandins"}],"container-title":["Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rep.bioscientifica.com\/view\/journals\/rep\/142\/2\/353.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/reproduction\/article-pdf\/142\/2\/353\/64534930\/353.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/reproduction\/article-pdf\/142\/2\/353\/64534930\/353.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T18:04:22Z","timestamp":1767809062000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/reproduction\/article\/142\/2\/353\/8243493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,8,1]]},"references-count":52,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2011,8,1]]}},"URL":"https:\/\/doi.org\/10.1530\/rep-11-0060","relation":{},"ISSN":["1470-1626","1741-7899"],"issn-type":[{"value":"1470-1626","type":"print"},{"value":"1741-7899","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,8,1]]},"published":{"date-parts":[[2011,8,1]]}}}