{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:08:52Z","timestamp":1790431732556,"version":"4.1.0"},"reference-count":81,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["HD096057"],"award-info":[{"award-number":["HD096057"]}]},{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["HD032067"],"award-info":[{"award-number":["HD032067"]}]},{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["NGP10125"],"award-info":[{"award-number":["NGP10125"]}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["HD096057"],"award-info":[{"award-number":["HD096057"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["HD032067"],"award-info":[{"award-number":["HD032067"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["NGP10125"],"award-info":[{"award-number":["NGP10125"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The uterus plays an essential role in the reproductive health of women and controls critical processes such as embryo implantation, placental development, parturition, and menstruation. Progesterone receptor (PR) regulates key aspects of the reproductive function of several mammalian species by directing the transcriptional program in response to progesterone (P4). P4\/PR signaling controls endometrial receptivity and decidualization during early pregnancy and is critical for the establishment and outcome of a successful pregnancy. PR is also essential throughout gestation and during labor, and it exerts critical roles in the myometrium, mainly by the specialized function of its two isoforms, progesterone receptor A (PR-A) and progesterone receptor B (PR-B), which display distinct and separate roles as regulators of transcription. This review summarizes recent studies related to the roles of PR function in the decidua and myometrial tissues. We discuss how PR acquired key features in placental mammals that resulted in a highly specialized and dynamic role in the decidua. We also summarize recent literature that evaluates the myometrial PR-A\/PR-B ratio at parturition and discuss the efficacy of current treatment options for preterm birth.<\/jats:p>","DOI":"10.3390\/cells11091474","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T13:40:57Z","timestamp":1651066857000},"page":"1474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Progesterone Receptor Signaling in the Uterus Is Essential for Pregnancy Success"],"prefix":"10.3390","volume":"11","author":[{"given":"Dominique","family":"Cope","sequence":"first","affiliation":[{"name":"Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Center for Drug Discovery, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5660-6392","authenticated-orcid":false,"given":"Diana","family":"Monsivais","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Center for Drug Discovery, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1071\/RD9951003","article-title":"Monotreme and marsupial reproduction","volume":"7","author":"Renfree","year":"1995","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e27450","DOI":"10.7554\/eLife.27450","article-title":"Molecular conservation of marsupial and eutherian placentation and lactation","volume":"6","author":"Guernsey","year":"2017","journal-title":"eLife"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1387\/ijdb.130335gw","article-title":"Evolution of mammalian pregnancy and the origin of the decidual stromal cell","volume":"58","author":"Wagner","year":"2014","journal-title":"Int. J. Dev. Biol."},{"key":"ref_4","first-page":"7","article-title":"Structural changes in vertebrate fetal membranes associated with the adoption of viviparity","volume":"3","author":"Mossman","year":"1974","journal-title":"Obstet. Gynecol. Annu."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ng, S.-W., Norwitz, G.A., Pavlicev, M., Tilburgs, T., Sim\u00f3n, C., and Norwitz, E.R. (2020). Endometrial Decidualization: The Primary Driver of Pregnancy Health. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21114092"},{"key":"ref_6","first-page":"95","article-title":"Decidualization score identifies an endometrial dysregulation in samples from women with recurrent pregnancy losses and unexplained infertility","volume":"2","author":"Dambaeva","year":"2020","journal-title":"F S Rep."},{"key":"ref_7","first-page":"E8468","article-title":"Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology","volume":"114","author":"Dominguez","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.celrep.2014.12.052","article-title":"Ancient Transposable Elements Transformed the Uterine Regulatory Landscape and Transcriptome during the Evolution of Mammalian Pregnancy","volume":"10","author":"Lynch","year":"2015","journal-title":"Cell Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e61257","DOI":"10.7554\/eLife.61257","article-title":"Evolutionary transcriptomics implicates HAND2 in the origins of implantation and regulation of gestation length","volume":"10","author":"Mika","year":"2021","journal-title":"eLife"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/s41576-021-00385-1","article-title":"Transposable elements shape the evolution of mammalian development","volume":"22","author":"Senft","year":"2021","journal-title":"Nat. Rev. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/biolre\/ioab183","article-title":"Single-cell analysis of prostaglandin E2-induced human decidual cell in vitro differentiation: A minimal ancestral deciduogenic signal","volume":"106","author":"Stadtmauer","year":"2021","journal-title":"Biol. Reprod."},{"key":"ref_12","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":"ref_13","first-page":"2743","article-title":"Ovarian carcinoma-associated TaqI restriction fragment length polymorphism in intron G of the progesterone receptor gene is due to an Alu sequence insertion","volume":"55","author":"Rowe","year":"1995","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1186\/gb-2011-12-12-236","article-title":"Alu elements: Know the SINEs","volume":"12","author":"Deininger","year":"2011","journal-title":"Genome Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6340","DOI":"10.1210\/jc.2004-0114","article-title":"A Germline Variation in the Progesterone Receptor Gene Increases Transcriptional Activity and May Modify Ovarian Cancer Risk","volume":"89","author":"Agoulnik","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1677\/jme.1.02170","article-title":"The PROGINS polymorphism of the human progesterone receptor diminishes the response to progesterone","volume":"38","author":"Romano","year":"2007","journal-title":"J. Mol. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Langmia, I.M., Apalasamy, Y.D., Omar, S.Z., and Mohamed, Z. (2015). Progesterone Receptor (PGR) gene polymorphism is associated with susceptibility to preterm birth. BMC Med. Genet., 16.","DOI":"10.1186\/s12881-015-0202-1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1097\/AOG.0b013e3181d53b83","article-title":"Progesterone Receptor Genotype, Family History, and Spontaneous Preterm Birth","volume":"115","author":"Manuck","year":"2010","journal-title":"Obstet. Gynecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1093\/molbev\/msaa119","article-title":"The Neandertal Progesterone Receptor","volume":"37","author":"Zeberg","year":"2020","journal-title":"Mol. Biol. Evol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ajhg.2018.05.009","article-title":"Natural Selection Has Differentiated the Progesterone Receptor among Human Populations","volume":"103","author":"Li","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0303-7207(01)00465-8","article-title":"Reproductive functions of the progesterone receptor isoforms: Lessons from knock-out mice","volume":"179","author":"Conneely","year":"2001","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_22","first-page":"8356","article-title":"The A and B isoforms of the human progesterone receptor operate through distinct signaling pathways within target cells","volume":"14","author":"Wen","year":"1994","journal-title":"Mol. Cell. Biol."},{"key":"ref_23","first-page":"1347","article-title":"A third transactivation function (AF3) of human progesterone receptors located in the unique N-terminal segment of the B-isoform","volume":"8","author":"Sartorius","year":"1994","journal-title":"Mol. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1126\/science.289.5485.1751","article-title":"Subgroup of Reproductive Functions of Progesterone Mediated by Progesterone Receptor-B Isoform","volume":"289","author":"Mullinax","year":"2000","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9744","DOI":"10.1073\/pnas.1732707100","article-title":"Defective mammary gland morphogenesis in mice lacking the progesterone receptor B isoform","volume":"100","author":"Lydon","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1095\/biolreprod.116.144410","article-title":"Decreased epithelial progesterone receptor A at the window of receptivity is required for preparation of the endometrium for embryo attachment\u2020","volume":"96","author":"Wetendorf","year":"2017","journal-title":"Biol. Reprod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"103487","DOI":"10.1016\/j.isci.2021.103487","article-title":"The role of epithelial progesterone receptor isoforms in embryo implantation","volume":"24","author":"Li","year":"2021","journal-title":"iScience"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"eaaz9646","DOI":"10.1126\/scisignal.aaz9646","article-title":"Constitutive expression of progesterone receptor isoforms promotes the development of hormone-dependent ovarian neoplasms","volume":"13","author":"Wetendorf","year":"2020","journal-title":"Sci. Signal."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2011643118","DOI":"10.1073\/pnas.2011643118","article-title":"Progesterone receptor isoform B regulates the Oxtr-Plcl2-Trpc3 pathway to suppress uterine contractility","volume":"118","author":"Peavey","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e1419","DOI":"10.1210\/clinem\/dgz117","article-title":"Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators","volume":"105","author":"Chi","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1101\/gad.9.18.2266","article-title":"Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities","volume":"9","author":"Lydon","year":"1995","journal-title":"Genes Dev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.semcdb.2007.12.001","article-title":"In vivo analysis of progesterone receptor action in the uterus during embryo implantation","volume":"19","author":"Franco","year":"2008","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"12021","DOI":"10.1073\/pnas.96.21.12021","article-title":"Progesterone receptors in the thymus are required for thymic involution during pregnancy and for normal fertility","volume":"96","author":"Tibbetts","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"198","DOI":"10.3389\/fendo.2019.00198","article-title":"Progesterone-Related Immune Modulation of Pregnancy and Labor","volume":"10","author":"Shah","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/s41586-020-03071-0","article-title":"RANK links thymic regulatory T cells to fetal loss and gestational diabetes in pregnancy","volume":"589","author":"Paolino","year":"2020","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/humupd\/dmu056","article-title":"Role of nuclear progesterone receptor isoforms in uterine pathophysiology","volume":"21","author":"Patel","year":"2014","journal-title":"Hum. Reprod. Updat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1210\/me.2011-1355","article-title":"Research Resource: Genome-Wide Profiling of Progesterone Receptor Binding in the Mouse Uterus","volume":"26","author":"Rubel","year":"2012","journal-title":"Mol. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Yin, P., Roqueiro, D., Huang, L., Owen, J.K., Xie, A., Navarro, A., Monsivais, D., Coon, V.J.S., Kim, J.J., and Dai, Y. (2012). Genome-Wide Progesterone Receptor Binding: Cell Type-Specific and Shared Mechanisms in T47D Breast Cancer Cells and Primary Leiomyoma Cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029021"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1016\/j.stemcr.2021.07.013","article-title":"Progesterone receptor-DNA methylation crosstalk regulates depletion of uterine leiomyoma stem cells: A potential therapeutic target","volume":"16","author":"Liu","year":"2021","journal-title":"Stem Cell Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"bqaa143","DOI":"10.1210\/endocr\/bqaa143","article-title":"Targeting DNA Methylation Depletes Uterine Leiomyoma Stem Cell\u2013enriched Population by Stimulating Their Differentiation","volume":"161","author":"Liu","year":"2020","journal-title":"Endocrinology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"bqaa172","DOI":"10.1210\/endocr\/bqaa172","article-title":"Towards an Epigenetic Treatment of Leiomyomas?","volume":"161","author":"Vaiman","year":"2020","journal-title":"Endocrinology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4809","DOI":"10.1210\/endo.140.10.7070","article-title":"Progesterone Receptor Regulates Decidual Prolactin Expression in Differentiating Human Endometrial Stromal Cells1","volume":"140","author":"Brosens","year":"1999","journal-title":"Endocrinology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1210\/me.2014-1363","article-title":"Roles of Progesterone Receptor A and B Isoforms during Human Endometrial Decidualization","volume":"29","author":"Kaya","year":"2015","journal-title":"Mol. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1210\/en.2014-1566","article-title":"Progesterone Receptor Transcriptome and Cistrome in Decidualized Human Endometrial Stromal Cells","volume":"156","author":"Mazur","year":"2015","journal-title":"Endocrinology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"bqaa070","DOI":"10.1210\/endocr\/bqaa070","article-title":"GATA2 and Progesterone Receptor Interaction in Endometrial Stromal Cells Undergoing Decidualization","volume":"161","author":"Kohlmeier","year":"2020","journal-title":"Endocrinology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"16272","DOI":"10.1073\/pnas.0603002103","article-title":"Regulation of the SUMO pathway sensitizes differentiating human endometrial stromal cells to progesterone","volume":"103","author":"Jones","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"39261","DOI":"10.1074\/jbc.R300024200","article-title":"Unfolding the Action of Progesterone Receptors","volume":"278","author":"Li","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9099","DOI":"10.1074\/jbc.M805226200","article-title":"Mechanisms Underlying the Control of Progesterone Receptor Transcriptional Activity by SUMOylation","volume":"284","author":"Dudevoir","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"176701","DOI":"10.1242\/dev.176701","article-title":"Loss of the E2 SUMO-conjugating enzyme Ube2i in oocytes during ovarian folliculogenesis causes infertility in mice","volume":"146","author":"Rodriguez","year":"2019","journal-title":"Development"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00441-015-2286-5","article-title":"Regulation of germ cell function by SUMOylation","volume":"363","author":"Rodriguez","year":"2015","journal-title":"Cell Tissue Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e70753","DOI":"10.7554\/eLife.70753","article-title":"Disrupted PGR-B and ESR1 signaling underlies defective decidualization linked to severe preeclampsia","volume":"10","author":"Cordero","year":"2021","journal-title":"eLife"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Practice Committee of American Society for Reproductive Medicine (2013). Definitions of infertility and recurrent pregnancy loss: A committee opinion. Fertil. Steril., 99, 63.","DOI":"10.1016\/j.fertnstert.2012.09.023"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.jri.2015.01.007","article-title":"Immune profiling in patients with recurrent miscarriage","volume":"108","author":"Kuon","year":"2015","journal-title":"J. Reprod. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1111\/1471-0528.14949","article-title":"Genetic variation in the progesterone receptor gene and susceptibility to recurrent pregnancy loss: A case-control study","volume":"125","author":"Bahia","year":"2017","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e8712","DOI":"10.1371\/journal.pone.0008712","article-title":"Role of Progesterone Receptor Polymorphisms in the Recurrent Spontaneous Abortions: Indian Case","volume":"5","author":"Aruna","year":"2010","journal-title":"PLoS ONE"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s10815-010-9510-8","article-title":"Association of progesterone receptor polymorphism with idiopathic recurrent pregnancy loss in Taiwanese Han population","volume":"28","author":"Su","year":"2010","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1067\/S0002-9378(03)00517-9","article-title":"Human progesterone receptor polymorphisms and implantation failure during in vitro fertilization","volume":"189","author":"Cramer","year":"2003","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"11565","DOI":"10.1038\/ncomms11565","article-title":"Molecular evidence of functional progesterone withdrawal in human myometrium","volume":"7","author":"Nadeem","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1073\/pnas.54.4.1069","article-title":"The effect of progesterone on the human uterus","volume":"54","author":"Csapo","year":"1965","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1073\/pnas.67.2.501","article-title":"Progesterone \u201cReceptors\u201d in the Cytoplasm and Nucleus of Chick Oviduct Target Tissue","volume":"67","author":"Sherman","year":"1970","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.jsgi.2003.12.004","article-title":"Myometrial Progesterone responsiveness and the Control of Human Parturition","volume":"11","author":"Mesiano","year":"2004","journal-title":"J. Soc. Gynecol. Investig."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/bs.ctdb.2017.03.001","article-title":"Progesterone Receptor Signaling in Uterine Myometrial Physiology and Preterm Birth","volume":"125","author":"Wu","year":"2017","journal-title":"Curr. Top Dev. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e37","DOI":"10.1016\/S2214-109X(18)30451-0","article-title":"Global, regional, and national estimates of levels of preterm birth in 2014: A systematic review and modelling analysis","volume":"7","author":"Chawanpaiboon","year":"2018","journal-title":"Lancet Glob. Health"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"E719","DOI":"10.1210\/jc.2011-3251","article-title":"Progesterone Receptor-A and -B Have Opposite Effects on Proinflammatory Gene Expression in Human Myometrial Cells: Implications for Progesterone Actions in Human Pregnancy and Parturition","volume":"97","author":"Tan","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.bpobgyn.2018.08.006","article-title":"Efficacy of progesterone for prevention of preterm birth","volume":"52","author":"Sykes","year":"2018","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.ajog.2013.04.027","article-title":"Progesterone is not the same as 17\u03b1-hydroxyprogesterone caproate: Implications for obstetrical practice","volume":"208","author":"Romero","year":"2013","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1002\/ijgo.13852","article-title":"FIGO good practice recommendations on progestogens for prevention of preterm delivery","volume":"155","author":"Shennan","year":"2021","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1056\/NEJMoa035140","article-title":"Prevention of Recurrent Preterm Delivery by 17 Alpha-Hydroxyprogesterone Caproate","volume":"348","author":"Meis","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1055\/s-0039-3400227","article-title":"17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial","volume":"37","author":"Blackwell","year":"2020","journal-title":"Am. J. Perinatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1016\/S0140-6736(16)00350-0","article-title":"Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): A multicentre, randomised, double-blind trial","volume":"387","author":"Norman","year":"2016","journal-title":"Lancet"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/ijgo.13187","article-title":"Progesterone and preterm birth","volume":"150","author":"Norman","year":"2020","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_72","first-page":"CD004947","article-title":"Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth","volume":"7","author":"Dodd","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1016\/S0140-6736(09)60947-8","article-title":"Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): A randomised, double-blind, placebo-controlled study and meta-analysis","volume":"373","author":"Norman","year":"2009","journal-title":"Lancet"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"86.e1","DOI":"10.1016\/j.ajog.2020.06.050","article-title":"Early vaginal progesterone versus placebo in twin pregnancies for the prevention of spontaneous preterm birth: A randomized, double-blind trial","volume":"224","author":"Rehal","year":"2020","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1002\/uog.9093","article-title":"Prevention of preterm delivery in twin gestations (PREDICT): A multicenter, randomized, placebo-controlled trial on the effect of vaginal micronized progesterone","volume":"38","author":"Rode","year":"2011","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s40748-021-00135-5","article-title":"Outcomes of multiple gestation births compared to singleton: Analysis of multicenter KID database","volume":"7","author":"Thekkeveedu","year":"2021","journal-title":"Matern. Health Neonatol. Perinatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1177\/1933719115625848","article-title":"Histone Deacetylase 1 Regulates the Expression of Progesterone Receptor A During Human Parturition by Occupying the Progesterone Receptor A Promoter","volume":"23","author":"Ke","year":"2016","journal-title":"Reprod. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1210\/me.2004-0302","article-title":"Regulation of Progesterone Levels during Pregnancy and Parturition by Signal Transducer and Activator of Transcription 5 and 20\u03b1-Hydroxysteroid Dehydrogenase","volume":"19","author":"Piekorz","year":"2005","journal-title":"Mol. Endocrinol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"7529","DOI":"10.1073\/pnas.1200650109","article-title":"MicroRNA-200a serves a key role in the decline of progesterone receptor function leading to term and preterm labor","volume":"109","author":"Williams","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"6773","DOI":"10.1111\/jcmm.16681","article-title":"Pro-inflammatory signals induce 20\u03b1-HSD expression in myometrial cells: A key mechanism for local progesterone withdrawal","volume":"25","author":"Nadeem","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"249.e1","DOI":"10.1016\/j.ajog.2021.08.013","article-title":"The selective progesterone receptor modulator-promegestone-delays term parturition and prevents systemic inflammation-mediated preterm birth in mice","volume":"226","author":"Shynlova","year":"2021","journal-title":"Am. J. Obstet. Gynecol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/9\/1474\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:01:53Z","timestamp":1760137313000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/9\/1474"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,27]]},"references-count":81,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["cells11091474"],"URL":"https:\/\/doi.org\/10.3390\/cells11091474","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,27]]}}}