{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:38:03Z","timestamp":1792201083873,"version":"4.4.0"},"reference-count":55,"publisher":"The Endocrine Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Improved care of infants born prematurely has increased their survival. However, the incidence of preterm labor has not changed. To understand the processes involved in preterm labor, we used oligonucleotide microarrays to study gene expression in murine and human uterus during pregnancy. The induction of enzymes for prostaglandin synthesis was used as a marker for important changes during pregnancy because prostaglandins strongly contribute to both human and murine labor. We identified 504 genes that changed at least 2-fold between d 13.5 and 19.0 in the gravid mouse uterus. In the pregnant human myometrium, we found 478 genes that changed at least 2-fold in either term or preterm labor compared with preterm nonlabor specimens and 77 genes that significantly varied in both preterm and term labor. Patterns of gene regulation within functional groups comparing human preterm and term labor were similar, although the magnitude of change often varied. Surprisingly, few genes that changed significantly throughout pregnancy were the same in the mouse and human. These data suggest that functional progesterone withdrawal in human myometrium may not be the primary mechanism for labor induction, may implicate similar mechanisms for idiopathic preterm and term labor in humans, and may identify novel targets for further study.<\/jats:p>","DOI":"10.1210\/me.2003-0007","type":"journal-article","created":{"date-parts":[[2003,6,4]],"date-time":"2003-06-04T01:22:18Z","timestamp":1054689738000},"page":"1454-1469","source":"Crossref","is-referenced-by-count":117,"title":["Microarray Analysis of Uterine Gene Expression in Mouse and Human Pregnancy"],"prefix":"10.1210","volume":"17","author":[{"given":"Kathleen E.","family":"Bethin","sequence":"first","affiliation":[{"name":"Departments of Pediatrics (K.E.B., M.A., L.J.M.), St. Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Nagai","sequence":"additional","affiliation":[{"name":"Montreal Genome Centre (Y.N., R.S., T.J.H.), McGill University Health Centre, Montreal, Quebec, Canada H3A 2B4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Sladek","sequence":"additional","affiliation":[{"name":"Montreal Genome Centre (Y.N., R.S., T.J.H.), McGill University Health Centre, Montreal, Quebec, Canada H3A 2B4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Asada","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics (K.E.B., M.A., L.J.M.), St. Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoel","family":"Sadovsky","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology (Y.S., L.J.M.), St. Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Hudson","sequence":"additional","affiliation":[{"name":"Montreal Genome Centre (Y.N., R.S., T.J.H.), McGill University Health Centre, Montreal, Quebec, Canada H3A 2B4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis J.","family":"Muglia","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics (K.E.B., M.A., L.J.M.), St. Louis, Missouri 63110"},{"name":"Obstetrics and Gynecology (Y.S., L.J.M.), St. Louis, Missouri 63110"},{"name":"Molecular Biology and Pharmacology (L.J.M.), Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071614190701000_R1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1001\/jama.1995.03520290065031","article-title":"NIH Consensus Developmental Panel of the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes","volume":"273","year":"1995","journal-title":"JAMA"},{"key":"2020071614190701000_R2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1471-0528.1990.tb01711.x","article-title":"The effects of corticosteroid administration before preterm delivery: an overview of evidence from controlled trials.","volume":"97","author":"Crowley","year":"1990","journal-title":"Br J Obstet Gynecol"},{"key":"2020071614190701000_R3","first-page":"1","article-title":"The American College of Obstetrics and Gynecologists","volume":"206","year":"1995","journal-title":"ACOG Tech Bull"},{"key":"2020071614190701000_R4","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1126\/science.277.5326.681","article-title":"Failure of parturition in mice lacking the prostaglandin F receptor.","volume":"277","author":"Sugimoto","year":"1997","journal-title":"Science"},{"key":"2020071614190701000_R5","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/37622","article-title":"Role of cytoplasmic phospholipase A2 in allergic response and parturition.","volume":"390","author":"Uozumi","year":"1997","journal-title":"Nature"},{"key":"2020071614190701000_R6","doi-asserted-by":"crossref","first-page":"11871","DOI":"10.1073\/pnas.95.20.11875","article-title":"Opposing actions of prostaglandins and oxytocin determine the onset of murine labor.","volume":"95","author":"Gross","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614190701000_R7","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/j.1749-6632.1997.tb48546.x","article-title":"Prostaglandins and parturition.","volume":"828","author":"Challis","year":"1997","journal-title":"Ann NY Acad Sci"},{"key":"2020071614190701000_R8","first-page":"985","article-title":"Parturition.","author":"Challis","year":"1994","journal-title":"The physiology of reproduction"},{"key":"2020071614190701000_R9","first-page":"45","article-title":"Role of prostaglandins, prostacyclin, and thromboxanes in the physiologic control of the uterus and in parturition.","volume":"4","author":"Novy","year":"1980","journal-title":"Semin Perinatol"},{"key":"2020071614190701000_R10","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1126\/science.282.5389.699","article-title":"The transcriptional program of sporulation in budding yeast.","volume":"282","author":"Chu","year":"1998","journal-title":"Science"},{"key":"2020071614190701000_R11","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1126\/science.286.5439.531","article-title":"Molecular classification of cancer: class discovery and class prediction by gene expression monitoring.","volume":"286","author":"Golub","year":"1999","journal-title":"Science"},{"key":"2020071614190701000_R12","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1073\/pnas.98.3.1176","article-title":"Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer.","volume":"98","author":"Welsh","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614190701000_R13","first-page":"88","article-title":"Gene knockout mice in the study of parturition.","volume":"7","author":"Gross","year":"2000","journal-title":"J Soc Gynecol Invest"},{"key":"2020071614190701000_R14","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/S0002-9378(94)70284-5","article-title":"Expression of the gap junction protein connexin-43 is increased in the human myometrium toward term and with the onset of labor.","volume":"170","author":"Chow","year":"1994","journal-title":"Am J Obstet Gynecol"},{"key":"2020071614190701000_R15","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1071\/RD9950603","article-title":"Myometrial transcriptional regulation of the gap junction gene, connexin-43.","volume":"7","author":"Lefebvre","year":"1995","journal-title":"Reprod Fertil Dev"},{"key":"2020071614190701000_R16","first-page":"191","article-title":"The role of oxytocin in the initiation of labour and oxytocin-prostaglandin interactions.","author":"Soloff","year":"1988","journal-title":"The onset of labour: cellular and integrative mechanisms."},{"key":"2020071614190701000_R17","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1006\/geno.1998.5681","article-title":"Genomic organization of the human ELF3 (ESE-1\/ESX) gene, a member of the Ets transcription factor family, and identification of a functional promoter.","volume":"55","author":"Oettgen","year":"1999","journal-title":"Genomics"},{"key":"2020071614190701000_R18","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1677\/jme.0.0220295","article-title":"Regulation of the expression and activity by progestins of a member of the SOX gene family of transcriptional modulators.","volume":"22","author":"Graham","year":"1999","journal-title":"J Mol Endocrinol"},{"key":"2020071614190701000_R19","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1095\/biolreprod61.2.476","article-title":"Expression and hormonal regulation of the Sox4 gene in mouse female reproductive tissues.","volume":"61","author":"Hunt","year":"1999","journal-title":"Biol Reprod"},{"key":"2020071614190701000_R20","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/380711a0","article-title":"Defects in cardiac outflow tract formation and pro-B-lymphocyte expansion in mice lacking Sox-4.","volume":"380","author":"Schilham","year":"1996","journal-title":"Nature"},{"key":"2020071614190701000_R21","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/0092-8674(92)90592-Z","article-title":"Pleiotropic effects of a null mutation in the c-fos proto-oncogene.","volume":"71","author":"Johnson","year":"1992","journal-title":"Cell"},{"key":"2020071614190701000_R22","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1101\/gad.9.6.650","article-title":"p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene.","volume":"9","author":"Matsuoka","year":"1995","journal-title":"Genes Dev"},{"key":"2020071614190701000_R23","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1093\/oxfordjournals.jbchem.a022586","article-title":"Mice lacking a CDK inhibitor, p57Kip2, exhibit skeletal abnormalities and growth retardation.","volume":"127","author":"Takahashi","year":"2000","journal-title":"J Biochem"},{"key":"2020071614190701000_R24","first-page":"2189","article-title":"High cancer cell death in syngeneic tumors developed in host mice deficient for the stromelysin-3 matrix metalloproteinase.","volume":"61","author":"Boulay","year":"2001","journal-title":"Cancer Res"},{"key":"2020071614190701000_R25","doi-asserted-by":"crossref","first-page":"4902","DOI":"10.1210\/endo.138.11.5478","article-title":"Coordinate expression of matrix metalloproteinase family members in the uterus of normal, matrilysin-deficient, and stromelysin-1-deficient mice.","volume":"138","author":"Rudolph-Owen","year":"1997","journal-title":"Endocrinology"},{"key":"2020071614190701000_R26","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/0003-9861(92)90411-O","article-title":"Prostaglandin endoperoxide synthase gene structure: identification of the transcriptional start site and 5\u2032-flanking regulatory sequences.","volume":"293","author":"Kraemer","year":"1992","journal-title":"Arch Biochem Biophys"},{"key":"2020071614190701000_R27","doi-asserted-by":"crossref","first-page":"17520","DOI":"10.1074\/jbc.M110434200","article-title":"Activation of the murine type II transforming growth factor-\u03b2 receptor gene: up-regulation and function of the transcription factor Elf-3\/Ert\/Esx\/Ese-1.","volume":"277","author":"Kim","year":"2002","journal-title":"J Biol Chem"},{"key":"2020071614190701000_R28","first-page":"1177","article-title":"Elevated connexin-43 expression in term human myometrium correlates with elevated c-Jun expression and is independent of myometrial estrogen receptors.","volume":"83","author":"Geimonen","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614190701000_R29","doi-asserted-by":"crossref","first-page":"552","DOI":"10.3346\/jkms.1999.14.5.552","article-title":"Induction of c-Jun mRNA without changes of estrogen and progesterone receptor expression in myometrium during human labor.","volume":"14","author":"Roh","year":"1999","journal-title":"J Korean Med Sci"},{"key":"2020071614190701000_R30","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/37635","article-title":"Reduced fertility and postischaemic brain injury in mice deficient in cytosolic phospholipase A2.","volume":"390","author":"Bonventre","year":"1997","journal-title":"Nature"},{"key":"2020071614190701000_R31","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/0092-8674(95)90126-4","article-title":"Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration.","volume":"83","author":"Langenbach","year":"1995","journal-title":"Cell"},{"key":"2020071614190701000_R32","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1210\/endo.143.7.8926","article-title":"Coordinate regulation of prostaglandin metabolism for induction of parturition in mice.","volume":"143","author":"Winchester","year":"2002","journal-title":"Endocrinology"},{"key":"2020071614190701000_R33","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/S0002-9378(00)70226-2","article-title":"Effective diminution of amniotic prostaglandin production by selective inhibitors of cyclooxygenase type 2.","volume":"182","author":"Sadovsky","year":"2000","journal-title":"Am J Obstet Gynecol"},{"key":"2020071614190701000_R34","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0140-6736(05)62229-5","article-title":"Use of a cyclo-oxygenase type-2-selective non-steroidal anti-inflammatory agent to prevent preterm delivery.","volume":"350","author":"Sawdy","year":"1997","journal-title":"Lancet"},{"key":"2020071614190701000_R35","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1097\/00006254-199307000-00026","article-title":"Prostaglandin synthetase inhibitors in pregnancy.","volume":"48","author":"Van den Veyver","year":"1993","journal-title":"Obstet Gynecol Surv"},{"key":"2020071614190701000_R36","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0303-7207(95)03759-4","article-title":"C-fos and c-jun expression in human endometrium and myometrium.","volume":"117","author":"Salmi","year":"1996","journal-title":"Mol Cell Endocrinol"},{"key":"2020071614190701000_R37","doi-asserted-by":"crossref","first-page":"5468","DOI":"10.1210\/endo.137.12.8940373","article-title":"Temporal and cell-type specific expression of c-fos and c-jun protooncogenes in the mouse uterus after estrogen stimulation.","volume":"137","author":"Yamashita","year":"1996","journal-title":"Endocrinology"},{"key":"2020071614190701000_R38","doi-asserted-by":"crossref","first-page":"3571","DOI":"10.1210\/endo.136.8.7628395","article-title":"Increase in messenger ribonucleic acid encoding the myometrial gap junction protein, connexin-43, requires protein synthesis and is associated with increased expression of the activator protein-1, c-fos.","volume":"136","author":"Piersanti","year":"1995","journal-title":"Endocrinology"},{"key":"2020071614190701000_R39","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1093\/nar\/25.15.2953","article-title":"The world according to Maf.","volume":"25","author":"Motohashi","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"2020071614190701000_R40","doi-asserted-by":"crossref","first-page":"21162","DOI":"10.1074\/jbc.274.30.21162","article-title":"Characterization of the murine mafF gene.","volume":"274","author":"Onodera","year":"1999","journal-title":"J Biol Chem"},{"key":"2020071614190701000_R41","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1006\/bbrc.1999.1487","article-title":"Molecular cloning of a human MafF homologue, which specifically binds to the oxytocin receptor gene in term myometrium.","volume":"264","author":"Kimura","year":"1999","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071614190701000_R42","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s004390050573","article-title":"New p57KIP2 mutations in Beckwith-Wiedemann syndrome.","volume":"100","author":"Hatada","year":"1997","journal-title":"Hum Genet"},{"key":"2020071614190701000_R43","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1093\/hmg\/10.15.1601","article-title":"Distant cis-elements regulate imprinted expression of the mouse p57(Kip2) (Cdkn1c) gene: implications for the human disorder, Beckwith-Wiedemann syndrome.","volume":"10","author":"John","year":"2001","journal-title":"Hum Mol Genet"},{"key":"2020071614190701000_R44","doi-asserted-by":"crossref","first-page":"5279","DOI":"10.1073\/pnas.080409297","article-title":"Increased IGF-II protein affects p57kip2 expression in vivo and in vitro: implications for Beckwith-Wiedemann syndrome.","volume":"97","author":"Grandjean","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614190701000_R45","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/ng1095-204","article-title":"Genomic imprinting of p57KIP2, a cyclin-dependent kinase inhibitor, in mouse.","volume":"11","author":"Hatada","year":"1995","journal-title":"Nat Genet"},{"key":"2020071614190701000_R46","first-page":"125","article-title":"Progesterone receptor localization and isoforms in myometrium, decidua, and fetal membranes from rhesus macaques: evidence for functional progesterone withdrawal at parturition.","volume":"9","author":"Haluska","year":"2002","journal-title":"J Soc Gynecol Invest"},{"key":"2020071614190701000_R47","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1210\/jcem.87.6.8609","article-title":"Progesterone withdrawal and estrogen activation in human parturition are coordinated by progesterone receptor A expression in the myometrium.","volume":"87","author":"Mesiano","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614190701000_R48","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1179\/014788889794651870","article-title":"A complete protocol for in situ hybridization of messenger RNAs in brain and other tissues with radiolabeled single-stranded RNA probes.","volume":"12","author":"Simmons","year":"1989","journal-title":"J Histotechnol"},{"key":"2020071614190701000_R49","doi-asserted-by":"crossref","first-page":"9317","DOI":"10.1073\/pnas.97.16.9317","article-title":"Interleukin-6 is an essential, corticotropin-releasing hormone-independent stimulator of the adrenal axis during immune system activation.","volume":"97","author":"Bethin","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614190701000_R50","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1006\/geno.2001.6675","article-title":"Characterization of variability in large-scale gene expression data: implications for study design.","volume":"79","author":"Novak","year":"2002","journal-title":"Genomics"},{"key":"2020071614190701000_R51","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing.","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Soc Series B"},{"key":"2020071614190701000_R52","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1210\/mend.16.6.0874","article-title":"Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation.","volume":"16","author":"Lin","year":"2002","journal-title":"Mol Endocrinol"},{"key":"2020071614190701000_R53","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/ng0502-19","article-title":"GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways.","volume":"31","author":"Dahlquist","year":"2002","journal-title":"Nat Genet"},{"key":"2020071614190701000_R54","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/0896-6273(91)90274-4","article-title":"The dopamine \u03b2-hydroxylase gene promoter directs expression of E. coli lacZ to sympathetic and other neurons in adult transgenic mice.","volume":"7","author":"Mercer","year":"1991","journal-title":"Neuron"},{"key":"2020071614190701000_R55","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/0896-6273(91)90275-5","article-title":"Some neuronal cell populations express human dopamine \u03b2-hydroxylase-lacZ transgenes transiently during embryonic development.","volume":"7","author":"Kapur","year":"1991","journal-title":"Neuron"}],"container-title":["Molecular Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/17\/8\/1454\/8964845\/mend1454.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/17\/8\/1454\/8964845\/mend1454.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T20:07:40Z","timestamp":1734034060000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mend\/article\/17\/8\/1454\/2747469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,8,1]]},"references-count":55,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2003,8,1]]}},"URL":"https:\/\/doi.org\/10.1210\/me.2003-0007","relation":{},"ISSN":["0888-8809","1944-9917"],"issn-type":[{"value":"0888-8809","type":"print"},{"value":"1944-9917","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,8,1]]}}}