{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T00:55:44Z","timestamp":1792889744804,"version":"4.5.0"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"19","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,5,8]]},"abstract":"<jats:p>\n                    During pregnancy, uterine quiescence is maintained by increased progesterone receptor (PR) activity, but labor is facilitated by a series of events that impair PR function. Previously, we discovered that miR-200 family members serve as progesterone (P\n                    <jats:sub>4<\/jats:sub>\n                    )-modulated activators of contraction-associated genes in the pregnant uterus. In this study, we identified a unique role for miR-200a to enhance the local metabolism of P\n                    <jats:sub>4<\/jats:sub>\n                    in myometrium and, thus, decrease PR function during the progression toward labor. miR-200a exerts this action by direct repression of STAT5b, a transcriptional repressor of the P\n                    <jats:sub>4<\/jats:sub>\n                    -metabolizing enzyme 20\u03b1-hydroxysteroid dehydrogenase (20\u03b1-HSD). We observed that miR-200a expression increased and STAT5b expression coordinately decreased in myometrium of mice as they progressed to labor and in laboring myometrium from pregnant women. These changes were associated with a dramatic increase in expression and activity of 20\u03b1-HSD in laboring myometrium from mouse and human. Notably, overexpression of miR-200a in cultured human myometrial cells (hTERT-HM) suppressed STAT5b and increased 20\u03b1-HSD mRNA levels. In uterine tissues of ovariectomized mice injected with P\n                    <jats:sub>4<\/jats:sub>\n                    , miR-200 expression was significantly decreased, STAT5b expression was up-regulated, and 20\u03b1-HSD mRNA was decreased, but in 15 d postcoitum pregnant mice injected with the PR antagonist RU486, preterm labor was associated with increased miR-200a, decreased STAT5b, and enhanced 20\u03b1-HSD expression. Taken together, these findings implicate miR-200a as an important regulator of increased local P\n                    <jats:sub>4<\/jats:sub>\n                    metabolism in the pregnant uterus near term and provide insight into the importance of miR-200s in the decline in PR function leading to labor.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1200650109","type":"journal-article","created":{"date-parts":[[2012,4,24]],"date-time":"2012-04-24T01:30:51Z","timestamp":1335231051000},"page":"7529-7534","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":138,"title":["MicroRNA-200a serves a key role in the decline of progesterone receptor function leading to term and preterm labor"],"prefix":"10.1073","volume":"109","author":[{"given":"Koriand\u2019r C.","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Biochemistry,"},{"name":"North Texas March of Dimes Birth Defects Center, University of Texas Southwestern Medical Center, Dallas, TX 75390; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora E.","family":"Renthal","sequence":"additional","affiliation":[{"name":"Department of Biochemistry,"},{"name":"North Texas March of Dimes Birth Defects Center, University of Texas Southwestern Medical Center, Dallas, TX 75390; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer C.","family":"Condon","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, PA 15260"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Gerard","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole R.","family":"Mendelson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry,"},{"name":"Department of Obstetrics and Gynecology,"},{"name":"North Texas March of Dimes Birth Defects Center, University of Texas Southwestern Medical Center, Dallas, TX 75390; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,4,23]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2009-0016"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra061360"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-95-5-1486"},{"key":"e_1_3_3_4_2","first-page":"514","article-title":"Endocrine and paracrine regulation of birth at term and preterm","volume":"21","author":"Challis JRG","year":"2000","unstructured":"JRG Challis, SG Matthews, W Gibb, SJ Lye, Endocrine and paracrine regulation of birth at term and preterm. 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