{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T07:20:51Z","timestamp":1767856851617,"version":"3.49.0"},"reference-count":29,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Uterine decidualization, a crucial process for implantation, is a tightly regulated process encompassing proliferation, differentiation, and polyploidization of uterine stromal cells. Hoxa (Homeobox A)-10, a homeobox transcription factor, is highly expressed in decidualizing stromal cells. Targeted gene deletion experiments have demonstrated marked infertility resulting from severely compromised decidualization in Hoxa-10\u2212\/\u2212 mice. However, the underlying mechanism by which Hoxa-10 regulates stromal cell differentiation remains poorly understood. Cyclin D3, a G1 phase cell-cycle regulatory protein involved in stromal cell proliferation and decidualization, is significantly reduced in Hoxa-10\u2212\/\u2212 mice. The expression of cyclin D3 in the pregnant mouse uterus parallels stromal cell decidualization. Here, we show that adenovirus-driven cyclin D3 replacement in Hoxa-10\u2212\/\u2212 mice improves stromal cell decidualization. To address our question of whether cyclin D3 replacement in Hoxa-10\u2212\/\u2212 mice can improve decidualization, both in vitro and in vivo studies were completed after the addition of cyclin D3 or empty (control) viral vectors. Immunostaining demonstrated increased proliferation and decidualization in both in vitro and in vivo studies, and in situ hybridization confirmed increased expression of decidualization markers in vivo. Placentation was demonstrated as well in vivo in the cyclin D3-replaced animals. However, fertility was not restored in Hoxa-10\u2212\/\u2212 mice after d 10 of pregnancy. Finally, we identified several downstream targets of cyclin D3 during decidualization in vitro via proteomics experiments, and these were confirmed using in situ hybridization in vivo. Collectively, these results demonstrate that cyclin D3 expression influences a host of genes involved in decidualization and can improve decidualization in Hoxa-10\u2212\/\u2212 mice.<\/jats:p>","DOI":"10.1210\/en.2012-1528","type":"journal-article","created":{"date-parts":[[2012,9,25]],"date-time":"2012-09-25T01:57:14Z","timestamp":1348538234000},"page":"5575-5586","source":"Crossref","is-referenced-by-count":33,"title":["Overexpression of Cyclin D3 Improves Decidualization Defects in Hoxa-10\u2212\/\u2212 Mice"],"prefix":"10.1210","volume":"153","author":[{"given":"Julie M.","family":"Sroga","sequence":"first","affiliation":[{"name":"Obstetrics and Gynecology (J.M.S.), University of Cincinnati, Cincinnati, Ohio 45267"},{"name":"Pediatrics (J.M.S., F.G., X.M., S.K.D.), Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Gao","sequence":"first","affiliation":[{"name":"Pediatrics (J.M.S., F.G., X.M., S.K.D.), Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229"},{"name":"Perinatal Institute (F.G., X.M., S.K.D.), Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinghong","family":"Ma","sequence":"first","affiliation":[{"name":"Pediatrics (J.M.S., F.G., X.M., S.K.D.), Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229"},{"name":"Perinatal Institute (F.G., X.M., S.K.D.), Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjoy K.","family":"Das","sequence":"first","affiliation":[{"name":"Pediatrics (J.M.S., F.G., X.M., S.K.D.), Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229"},{"name":"Perinatal Institute (F.G., X.M., S.K.D.), Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071613002663500_B1","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":"Vitam Horm"},{"key":"2020071613002663500_B2","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1210\/er.2003-0020","article-title":"Molecular cues to implantation.","volume":"25","author":"Dey","year":"2004","journal-title":"Endocr Rev"},{"key":"2020071613002663500_B3","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":"Mol Reprod Dev"},{"key":"2020071613002663500_B4","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1006\/dbio.1999.9206","article-title":"Zonula occludens-1 and E-cadherin are coordinately expressed in the mouse uterus with the initiation of implantation and decidualization.","volume":"208","author":"Paria","year":"1999","journal-title":"Dev Biol"},{"key":"2020071613002663500_B5","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0925-4773(01)00614-1","article-title":"Evidence for coordinated interaction of cyclin D3 with p21 and cdk6 in directing the development of uterine stromal cell decidualization and polyploidy during implantation.","volume":"111","author":"Tan","year":"2002","journal-title":"Mech Dev"},{"key":"2020071613002663500_B6","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":"Mol Endocrinol"},{"key":"2020071613002663500_B7","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1126\/science.1071601","article-title":"Deciphering the cross-talk of implantation: advances and challenges.","volume":"296","author":"Paria","year":"2002","journal-title":"Science"},{"key":"2020071613002663500_B8","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nrg1808","article-title":"Roadmap to embryo implantation: clues from mouse models.","volume":"7","author":"Wang","year":"2006","journal-title":"Nat Rev Genet"},{"key":"2020071613002663500_B9","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/374460a0","article-title":"Sexually dimorphic sterility phenotypes in Hoxa10-deficient mice.","volume":"374","author":"Satokata","year":"1995","journal-title":"Nature"},{"key":"2020071613002663500_B10","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0092-8674(94)90290-9","article-title":"Hox genes in vertebrate development.","volume":"78","author":"Krumlauf","year":"1994","journal-title":"Cell"},{"key":"2020071613002663500_B11","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0092-8674(92)90471-N","article-title":"Homeobox genes and axial patterning.","volume":"68","author":"McGinnis","year":"1992","journal-title":"Cell"},{"key":"2020071613002663500_B12","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1242\/dev.122.9.2687","article-title":"Mechanisms of reduced fertility in Hoxa-10 mutant mice: uterine homeosis and loss of maternal Hoxa-10 expression.","volume":"122","author":"Benson","year":"1996","journal-title":"Development"},{"key":"2020071613002663500_B13","doi-asserted-by":"crossref","first-page":"8185","DOI":"10.1073\/pnas.92.18.8185","article-title":"Cryptorchidism and homeotic transformations of spinal nerves and vertebrae in Hoxa-10 mutant mice.","volume":"92","author":"Rijli","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613002663500_B14","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1210\/endo-125-3-1683","article-title":"Cell type-specific localization of c-myc protein in the mouse uterus: modulation by steroid hormones and analysis of the periimplantation period.","volume":"125","author":"Huet-Hudson","year":"1989","journal-title":"Endocrinology"},{"key":"2020071613002663500_B15","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1210\/me.2003-0403","article-title":"Uterine Msx-1 and Wnt4 signaling becomes aberrant in mice with the loss of leukemia inhibitory factor or Hoxa-10: evidence for a novel cytokine-homeobox-Wnt signaling in implantation.","volume":"18","author":"Daikoku","year":"2004","journal-title":"Mol Endocrinol"},{"key":"2020071613002663500_B16","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":"J Clin Invest"},{"key":"2020071613002663500_B17","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":"Mol Hum Reprod"},{"key":"2020071613002663500_B18","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ydbio.2005.11.016","article-title":"Hoxa-10 deficiency alters region-specific gene expression and perturbs differentiation of natural killer cells during decidualization.","volume":"290","author":"Rahman","year":"2006","journal-title":"Dev Biol"},{"key":"2020071613002663500_B19","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1210\/me.2002-0290","article-title":"Gene expression profiling reveals progesterone-mediated cell cycle and immunoregulatory roles of Hoxa-10 in the preimplantation uterus.","volume":"17","author":"Yao","year":"2003","journal-title":"Mol Endocrinol"},{"key":"2020071613002663500_B20","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1677\/jme.0.0220091","article-title":"Cyclin D3 in the mouse uterus is associated with the decidualization process during early pregnancy.","volume":"22","author":"Das","year":"1999","journal-title":"J Mol Endocrinol"},{"key":"2020071613002663500_B21","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1210\/endo.136.4.7895677","article-title":"Differential expression and regulation of cytokine genes in the mouse uterus.","volume":"136","author":"Kover","year":"1995","journal-title":"Endocrinology"},{"key":"2020071613002663500_B22","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1073\/pnas.95.5.2509","article-title":"A simplified system for generating recombinant adenoviruses.","volume":"95","author":"He","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613002663500_B23","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/0092-8674(91)90101-4","article-title":"Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle.","volume":"65","author":"Matsushime","year":"1991","journal-title":"Cell"},{"key":"2020071613002663500_B24","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: a possible ligand for interaction with blastocyst EGF-receptor in implantation.","volume":"120","author":"Das","year":"1994","journal-title":"Development"},{"key":"2020071613002663500_B25","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1210\/me.2004-0332","article-title":"Proteomic analysis identifies immunophilin FK506 binding protein 4 (FKBP52) as a downstream target of Hoxa10 in the periimplantation mouse uterus.","volume":"19","author":"Daikoku","year":"2005","journal-title":"Mol Endocrinol"},{"key":"2020071613002663500_B26","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ydbio.2003.09.019","article-title":"HB-EGF directs stromal cell polyploidy and decidualization via cyclin D3 during implantation.","volume":"265","author":"Tan","year":"2004","journal-title":"Dev Biol"},{"key":"2020071613002663500_B27","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1530\/REP-08-0539","article-title":"Cell cycle regulatory control for uterine stromal cell decidualization in implantation.","volume":"137","author":"Das","year":"2009","journal-title":"Reproduction"},{"key":"2020071613002663500_B28","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/gene.20185","article-title":"Conditional gene recombination by adenovirus-driven Cre in the mouse uterus.","volume":"44","author":"Wang","year":"2006","journal-title":"Genesis"},{"key":"2020071613002663500_B29","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1093\/humrep\/14.5.1328","article-title":"HOX gene expression is altered in the endometrium of women with endometriosis.","volume":"14","author":"Taylor","year":"1999","journal-title":"Hum Reprod"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/153\/11\/5575\/10389268\/endo5575.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/153\/11\/5575\/10389268\/endo5575.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T15:11:03Z","timestamp":1643469063000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/153\/11\/5575\/2424544"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11,1]]},"references-count":29,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2012,11,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2012-1528","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,1]]}}}