{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:29:14Z","timestamp":1785522554816,"version":"3.56.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,5,4]],"date-time":"2024-05-04T00:00:00Z","timestamp":1714780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81671484"],"award-info":[{"award-number":["81671484"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Persistent and intense uterine contraction is a risk factor for preterm labor. We previously found that methyl-CpG-binding protein 2 (MeCP2), as a target of infection-related microRNA miR-212-3p, may play an inhibitory role in regulating myometrium contraction. However, the molecular mechanisms by which MeCP2 regulates myometrial contraction are still unknown. In this study, we found that MeCP2 protein expression was lower in myometrial specimens obtained from preterm labor cases, compared to those obtained from term labor cases. Herein, using RNA sequence analysis of global gene expression in human uterine smooth muscle cells (HUSMCs) following siMeCP2, we show that MeCP2 silencing caused dysregulation of the cholesterol metabolism pathway. Notably, MeCP2 silencing resulted in the upregulation of CYP27A1, the key enzyme involved in regulating cholesterol homeostasis, in HUSMCs. Methylation-specific PCR, chromatin immunoprecipitation, and dual luciferase reporter gene technology indicated that MeCP2 could bind to the methylated CYP27A1 promoter region and repress its transcription. Administration of siCYP27A1 in a lipopolysaccharide (LPS)-induced preterm labor mouse model delayed the onset of preterm labor. Human preterm myometrium and the LPS-induced preterm labor mouse model both showed lower expression of MeCP2 and increased expression of CYP27A1. These results demonstrated that aberrant upregulation of CYP27A1 induced by MeCP2 silencing is one of the mechanisms facilitating inappropriate myometrial contraction. CYP27A1 could be exploited as a novel therapeutic target for preterm birth.<\/jats:p>","DOI":"10.1093\/molehr\/gaae016","type":"journal-article","created":{"date-parts":[[2024,5,5]],"date-time":"2024-05-05T20:23:43Z","timestamp":1714940623000},"source":"Crossref","is-referenced-by-count":3,"title":["Methyl-CpG-binding protein 2 regulates CYP27A1-induced myometrial contraction during preterm labor"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6566-0454","authenticated-orcid":false,"given":"Ting","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Changning Maternity & Infant Health Hospital, East China Normal University , Shanghai, China"},{"name":"Department of Obstetrics, Shanghai Obstetrics and Gynecology Hospital of Fudan University , Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayan","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences,Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology , Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyun","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences,Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology , Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Shanghai Obstetrics and Gynecology Hospital of Fudan University , Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences,Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology , Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences,Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology , Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xixi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Shanghai Obstetrics and Gynecology Hospital of Fudan University , Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0698-1693","authenticated-orcid":false,"given":"Jin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences,Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology , Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,4]]},"reference":[{"key":"2024053019455452000_gaae016-B1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.placenta.2020.04.016","article-title":"Challenges in preterm birth research: Ghanaian perspective","volume":"98","author":"Adu-Bonsaffoh","year":"2020","journal-title":"Placenta"},{"key":"2024053019455452000_gaae016-B2","doi-asserted-by":"crossref","first-page":"472.e1","DOI":"10.1016\/j.ajog.2013.03.005","article-title":"A proposed method to predict preterm birth using clinical data, standard maternal serum screening, and cholesterol","volume":"208","author":"Alleman","year":"2013","journal-title":"Am J Obstet Gynecol"},{"key":"2024053019455452000_gaae016-B3","doi-asserted-by":"crossref","first-page":"e155","DOI":"10.1097\/AOG.0000000000001711","article-title":"Practice bulletin no. 171: management of preterm labor","volume":"128","author":"American College of Obstetricians and Gynecologists\u2019 Committee on Practice Bulletins\u2014Obstetrics","year":"2016","journal-title":"Obstet Gynecol"},{"key":"2024053019455452000_gaae016-B4","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1016\/S0002-9378(11)90806-0","article-title":"Gap junction formation in human myometrium: a key to preterm labor?","volume":"168","author":"Balducci","year":"1993","journal-title":"Am J Obstet Gynecol"},{"issue":"Suppl 1","key":"2024053019455452000_gaae016-B5","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/pr.2013.204","article-title":"Preterm birth-associated neurodevelopmental impairment estimates at regional and global levels for 2010","volume":"74","author":"Blencowe","year":"2013","journal-title":"Pediatr Res"},{"key":"2024053019455452000_gaae016-B6","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1126\/science.1153252","article-title":"MeCP2, a key contributor to neurological disease, activates and represses transcription","volume":"320","author":"Chahrour","year":"2008","journal-title":"Science"},{"key":"2024053019455452000_gaae016-B7","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":"2019","journal-title":"Lancet Glob Health"},{"key":"2024053019455452000_gaae016-B8","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.molp.2020.06.009","article-title":"TBtools: an integrative toolkit developed for interactive analyses of big biological data","volume":"13","author":"Chen","year":"2020","journal-title":"Mol Plant"},{"key":"2024053019455452000_gaae016-B9","first-page":"315","article-title":"Dystocia and augmentation of labor","volume":"85","author":"Committee on Practice Bulletins\u2014Obstetrics, American College of Obstetricians and Gynecologists","year":"2004","journal-title":"Int J Gynaecol Obstet"},{"key":"2024053019455452000_gaae016-B10","doi-asserted-by":"crossref","first-page":"e1226","DOI":"10.1016\/S2214-109X(21)00298-9","article-title":"Preterm births in China between 2012 and 2018: an observational study of more than 9 million women","volume":"9","author":"Deng","year":"2021","journal-title":"Lancet Glob Health"},{"key":"2024053019455452000_gaae016-B11","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1542\/peds.2006-1939","article-title":"Adverse birth outcome among mothers with low serum cholesterol","volume":"120","author":"Edison","year":"2007","journal-title":"Pediatrics"},{"key":"2024053019455452000_gaae016-B12","first-page":"CD002255","article-title":"Calcium channel blockers for inhibiting preterm labor and birth","volume":"2014","author":"Flenady","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"2024053019455452000_gaae016-B13","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0002-9378(16)32279-7","article-title":"Endocrine, structural, and functional changes in the uterus during premature labor","volume":"142","author":"Garfield","year":"1982","journal-title":"Am J Obstet Gynecol"},{"key":"2024053019455452000_gaae016-B14","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1067\/S0002-9378(03)00545-3","article-title":"Bile acids increase response and expression of human myometrial oxytocin receptor","volume":"189","author":"Germain","year":"2003","journal-title":"Am J Obstet Gynecol"},{"key":"2024053019455452000_gaae016-B15","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.maturitas.2017.07.014","article-title":"27-Hydroxycholesterol, an endogenous selective estrogen receptor modulator","volume":"104","author":"He","year":"2017","journal-title":"Maturitas"},{"key":"2024053019455452000_gaae016-B16","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.tins.2017.11.005","article-title":"MeCP2 as an activator of gene expression","volume":"41","author":"Horvath","year":"2018","journal-title":"Trends Neurosci"},{"key":"2024053019455452000_gaae016-B17","doi-asserted-by":"crossref","first-page":"581","DOI":"10.3109\/00016348609158391","article-title":"Maximal response to oxytocin of the isolated myometrium from pregnant patients with intrahepatic cholestasis","volume":"65","author":"Israel","year":"1986","journal-title":"Acta Obstet Gynecol Scand"},{"key":"2024053019455452000_gaae016-B18","doi-asserted-by":"crossref","first-page":"13859","DOI":"10.1074\/jbc.M111.309864","article-title":"Methyl CpG-binding protein isoform MeCP2_e2 is dispensable for Rett syndrome phenotypes but essential for embryo viability and placenta development","volume":"287","author":"Itoh","year":"2012","journal-title":"J Biol Chem"},{"key":"2024053019455452000_gaae016-B19","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/jp.2016.4","article-title":"Maternal apolipoprotein E genotype as a potential risk factor for poor birth outcomes: The Bogalusa Heart Study","volume":"36","author":"Jacobs","year":"2016","journal-title":"J Perinatol"},{"key":"2024053019455452000_gaae016-B20","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/561","article-title":"Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription","volume":"19","author":"Jones","year":"1998","journal-title":"Nat Genet"},{"key":"2024053019455452000_gaae016-B21","doi-asserted-by":"crossref","first-page":"151477","DOI":"10.1016\/j.semperi.2021.151477","article-title":"How can obstetricians improve outcomes for infants born extremely preterm?","volume":"45","author":"Kane","year":"2021","journal-title":"Semin Perinatol"},{"key":"2024053019455452000_gaae016-B22","doi-asserted-by":"crossref","first-page":"D457","DOI":"10.1093\/nar\/gkv1070","article-title":"KEGG as a reference resource for gene and protein annotation","volume":"44","author":"Kanehisa","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2024053019455452000_gaae016-B23","doi-asserted-by":"crossref","first-page":"577","DOI":"10.2174\/1381612825666190329124214","article-title":"Safety and efficacy of tocolytics for the treatment of spontaneous preterm labor","volume":"25","author":"Lamont","year":"2019","journal-title":"Curr Pharm Des"},{"key":"2024053019455452000_gaae016-B24","doi-asserted-by":"crossref","first-page":"6910","DOI":"10.1158\/0008-5472.CAN-05-0530","article-title":"Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery","volume":"65","author":"Landen","year":"2005","journal-title":"Cancer Res"},{"key":"2024053019455452000_gaae016-B25","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.4161\/cbt.5.12.3468","article-title":"Intraperitoneal delivery of liposomal siRNA for therapy of advanced ovarian cancer","volume":"5","author":"Landen","year":"2006","journal-title":"Cancer Biol Ther"},{"key":"2024053019455452000_gaae016-B26","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.1016\/S2214-109X(18)30484-4","article-title":"Small babies, big numbers: global estimates of preterm birth","volume":"7","author":"Lee","year":"2019","journal-title":"Lancet Glob Health"},{"key":"2024053019455452000_gaae016-B27","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1093\/bioinformatics\/18.11.1427","article-title":"MethPrimer: designing primers for methylation PCRs","volume":"18","author":"Li","year":"2002","journal-title":"Bioinformatics"},{"issue":"Suppl 1","key":"2024053019455452000_gaae016-B28","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1186\/1471-2393-7-S1-S2","article-title":"Overview. Preterm labor: mechanisms and management","volume":"7","author":"L\u00f3pez Bernal","year":"2007","journal-title":"BMC Pregnancy Childbirth"},{"key":"2024053019455452000_gaae016-B29","doi-asserted-by":"crossref","first-page":"114621","DOI":"10.1016\/j.bcp.2021.114621","article-title":"Our evolving understanding of how 27-hydroxycholesterol influences cancer","volume":"196","author":"Ma","year":"2022","journal-title":"Biochem Pharmacol"},{"key":"2024053019455452000_gaae016-B30","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.yhbeh.2018.02.007","article-title":"Placental CpG methylation of HPA-axis genes is associated with cognitive impairment at age 10 among children born extremely preterm","volume":"101","author":"Meakin","year":"2018","journal-title":"Horm Behav"},{"key":"2024053019455452000_gaae016-B31","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/ng1180","article-title":"PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes","volume":"34","author":"Mootha","year":"2003","journal-title":"Nat Genet"},{"key":"2024053019455452000_gaae016-B32","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/30764","article-title":"Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex","volume":"393","author":"Nan","year":"1998","journal-title":"Nature"},{"key":"2024053019455452000_gaae016-B33","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.clp.2019.02.001","article-title":"Drugs for the treatment and prevention of preterm labor","volume":"46","author":"Patel","year":"2019","journal-title":"Clin Perinatol"},{"key":"2024053019455452000_gaae016-B34","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S2352-4642(21)00311-4","article-title":"Global, regional, and national causes of under-5 mortality in 2000-19: an updated systematic analysis with implications for the Sustainable Development Goals","volume":"6","author":"Perin","year":"2022","journal-title":"Lancet Child Adolesc Health"},{"key":"2024053019455452000_gaae016-B35","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1083\/jcb.110.2.269","article-title":"Modulation of gap junction transcript and protein expression during pregnancy in the rat","volume":"110","author":"Risek","year":"1990","journal-title":"J Cell Biol"},{"key":"2024053019455452000_gaae016-B36","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024053019455452000_gaae016-B37","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":"2024053019455452000_gaae016-B38","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1093\/molehr\/gaz005","article-title":"Pro-inflammatory cytokine-induced microRNA-212-3p expression promotes myocyte contraction via methyl-CpG-binding protein 2: a novel mechanism for infection-related preterm parturition","volume":"25","author":"Tang","year":"2019","journal-title":"Mol Hum Reprod"},{"key":"2024053019455452000_gaae016-B39","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.placenta.2004.06.012","article-title":"Progesterone synthesis by the human placenta","volume":"26","author":"Tuckey","year":"2005","journal-title":"Placenta"},{"key":"2024053019455452000_gaae016-B40","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1038\/s41467-020-15923-4","article-title":"Dysregulation of bile acids increases the risk for preterm birth in pregnant women","volume":"11","author":"You","year":"2020","journal-title":"Nat Commun"}],"container-title":["Molecular Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/molehr\/advance-article-pdf\/doi\/10.1093\/molehr\/gaae016\/57405510\/gaae016.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/molehr\/article-pdf\/30\/6\/gaae016\/58011477\/gaae016.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/molehr\/article-pdf\/30\/6\/gaae016\/58011477\/gaae016.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T20:43:07Z","timestamp":1717101787000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/molehr\/article\/doi\/10.1093\/molehr\/gaae016\/7665157"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,4]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,5,30]]}},"URL":"https:\/\/doi.org\/10.1093\/molehr\/gaae016","relation":{},"ISSN":["1460-2407"],"issn-type":[{"value":"1460-2407","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,6,1]]},"published":{"date-parts":[[2024,5,4]]},"article-number":"gaae016"}}