{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:36:25Z","timestamp":1790433385720,"version":"4.1.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"48","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,11,30]]},"abstract":"<jats:p>\n                    Throughout most of pregnancy, uterine quiescence is maintained by increased progesterone receptor (PR) transcriptional activity, whereas spontaneous labor is initiated\/facilitated by a concerted series of biochemical events that activate inflammatory pathways and have a negative impact on PR function. In this study, we uncovered a previously undescribed regulatory pathway whereby micro-RNAs (miRNAs) serve as hormonally modulated and conserved mediators of contraction-associated genes in the pregnant uterus in the mouse and human. Using miRNA and gene expression microarray analyses of uterine tissues, we identified a conserved family of miRNAs, the miR-200 family, that is highly induced at term in both mice and humans as well as two coordinately down-regulated targets, zinc finger E-box binding homeobox proteins ZEB1 and ZEB2, which act as transcriptional repressors. We also observed up-regulation of the miR-200 family and down-regulation of ZEB1 and ZEB2 in two different mouse models of preterm labor. We further demonstrated that ZEB1 is directly up-regulated by the action of progesterone (P\n                    <jats:sub>4<\/jats:sub>\n                    )\/PR at the\n                    <jats:italic>ZEB1<\/jats:italic>\n                    promoter. Excitingly, we observed that ZEB1 and ZEB2 inhibit expression of the contraction-associated genes, oxytocin receptor and connexin-43, and block oxytocin-induced contractility in human myometrial cells. Together, these findings implicate the miR-200 family and their targets, ZEB1 and ZEB2, as unique P\n                    <jats:sub>4<\/jats:sub>\n                    \/PR-mediated regulators of uterine quiescence and contractility during pregnancy and labor and shed light on the molecular mechanisms involved in preterm birth.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1008301107","type":"journal-article","created":{"date-parts":[[2010,11,15]],"date-time":"2010-11-15T23:15:12Z","timestamp":1289862912000},"page":"20828-20833","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":261,"title":["miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor"],"prefix":"10.1073","volume":"107","author":[{"given":"Nora E.","family":"Renthal","sequence":"first","affiliation":[{"name":"Departments of aBiochemistry,"},{"name":"North Texas March of Dimes Birth Defects Center, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Cheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Departments of aBiochemistry,"},{"name":"North Texas March of Dimes Birth Defects Center, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koriand\u2019r C.","family":"Williams","sequence":"additional","affiliation":[{"name":"Departments of aBiochemistry,"},{"name":"North Texas March of Dimes Birth Defects Center, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Gerard","sequence":"additional","affiliation":[{"name":"Internal Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Prange-Kiel","sequence":"additional","affiliation":[{"name":"Cell Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole R.","family":"Mendelson","sequence":"additional","affiliation":[{"name":"Departments of aBiochemistry,"},{"name":"Obstetrics and Gynecology,"},{"name":"North Texas March of Dimes Birth Defects Center, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,11,15]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1210\/me.2009-0016","article-title":"Minireview: Fetal-maternal hormonal signaling in pregnancy and labor","volume":"23","author":"Mendelson CR","year":"2009","unstructured":"CR Mendelson, Minireview: Fetal-maternal hormonal signaling in pregnancy and labor. 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