{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:21:13Z","timestamp":1789708873957,"version":"4.0.1"},"reference-count":91,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011636","name":"March of Dimes","doi-asserted-by":"publisher","award":["Prematurity Research Center Ohio Collaborative Funding 07\/13-6\/18"],"award-info":[{"award-number":["Prematurity Research Center Ohio Collaborative Funding 07\/13-6\/18"]}],"id":[{"id":"10.13039\/100011636","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD091527"],"award-info":[{"award-number":["R01HD091527"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011636","name":"March of Dimes Prematurity Research Center Ohio Collaborative","doi-asserted-by":"publisher","award":["22-FY13-543 2017-2018"],"award-info":[{"award-number":["22-FY13-543 2017-2018"]}],"id":[{"id":"10.13039\/100011636","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Preterm birth is a global public health crisis which results in significant neonatal and maternal mortality. Yet little is known regarding the molecular mechanisms of idiopathic spontaneous preterm birth, and we have few diagnostic markers for adequate assessment of placental development and function. Previous studies of placental pathology and our transcriptomics studies suggest a role for placental maturity in idiopathic spontaneous preterm birth. It is known that placental DNA methylation changes over gestation. We hypothesized that if placental hypermaturity is present in our samples, we would observe a unique idiopathic spontaneous preterm birth DNA methylation profile potentially driving the gene expression differences we previously identified in our placental samples. Our results indicate the idiopathic spontaneous preterm birth DNA methylation pattern mimics the term birth methylation pattern suggesting hypermaturity. Only seven significant differentially methylated regions fitting the idiopathic spontaneous preterm birth specific (relative to the controls) profile were identified, indicating unusually high similarity in DNA methylation between idiopathic spontaneous preterm birth and term birth samples. We identified an additional 1,718 significantly methylated regions in our gestational age matched controls where the idiopathic spontaneous preterm birth DNA methylation pattern mimics the term birth methylation pattern, again indicating a striking level of similarity between the idiopathic spontaneous preterm birth and term birth samples. Pathway analysis of these regions revealed differences in genes within the WNT and Cadherin signaling pathways, both of which are essential in placental development and maturation. Taken together, these data demonstrate that the idiopathic spontaneous preterm birth samples display a hypermature methylation signature than expected given their respective gestational age which likely impacts birth timing.<\/jats:p>","DOI":"10.1371\/journal.pone.0279991","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T18:00:50Z","timestamp":1679594450000},"page":"e0279991","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Characterization of methylation profiles in spontaneous preterm birth placental villous tissue"],"prefix":"10.1371","volume":"18","author":[{"given":"Heather M.","family":"Brockway","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha L.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhas G.","family":"Kallapur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalin S.","family":"Buhimschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0301-8770","authenticated-orcid":true,"given":"Louis J.","family":"Muglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen N.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,3,23]]},"reference":[{"issue":"Suppl 1","key":"pone.0279991.ref001","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1186\/1742-4755-10-S1-S2","article-title":"Born Too Soon: The global epidemiology of 15 million preterm births.","volume":"10","author":"H Blencowe","year":"2013","journal-title":"Reproductive Health."},{"key":"pone.0279991.ref002","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":"S Chawanpaiboon","year":"2018","journal-title":"The Lancet Global Health"},{"issue":"8","key":"pone.0279991.ref003","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1053\/j.semperi.2015.09.005","article-title":"The genetics of preterm birth: Progress and promise.","volume":"39","author":"NK Monangi","year":"2015","journal-title":"Seminars in perinatology"},{"issue":"1663","key":"pone.0279991.ref004","doi-asserted-by":"crossref","first-page":"20140066","DOI":"10.1098\/rstb.2014.0066","article-title":"The placenta: a multifaceted, transient organ.","volume":"370","author":"GJ Burton","year":"2015","journal-title":"Philosophical Transactions of the Royal Society of London B: Biological Sciences"},{"issue":"7","key":"pone.0279991.ref005","doi-asserted-by":"crossref","first-page":"698","DOI":"10.5858\/arpa.2015-0225-CC","article-title":"Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement.","volume":"140","author":"TY Khong","year":"2016","journal-title":"Archives of Pathology & Laboratory Medicine."},{"issue":"2","key":"pone.0279991.ref006","doi-asserted-by":"crossref","first-page":"86","DOI":"10.5115\/acb.2012.45.2.86","article-title":"Vasculosyncytial membrane in relation to syncytial knots complicates the placenta in preeclampsia: a histomorphometrical study.","volume":"45","author":"DK Sankar","year":"2012","journal-title":"Anatomy & Cell Biology."},{"issue":"03","key":"pone.0279991.ref007","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1055\/s-0035-1570379","article-title":"Role of the Placenta in Preterm Birth: A Review.","volume":"33","author":"TK Morgan","year":"2016","journal-title":"American Journal of Perinatology"},{"key":"pone.0279991.ref008","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.placenta.2016.10.006","article-title":"Placental histology in spontaneous and indicated preterm birth: A case control study","volume":"48","author":"TA Nijman","year":"2016","journal-title":"Placenta"},{"issue":"4","key":"pone.0279991.ref009","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.ajog.2015.02.010","article-title":"The phenotype of spontaneous preterm birth: application of a clinical phenotyping tool","volume":"212","author":"TA Manuck","year":"2015","journal-title":"American Journal of Obstetrics and Gynecology"},{"issue":"6","key":"pone.0279991.ref010","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.ajog.2018.09.036","article-title":"The clinical heterogeneity of preeclampsia is related to both placental gene expression and placental histopathology","volume":"219","author":"SJ Benton","year":"2018","journal-title":"American journal of obstetrics and gynecology"},{"issue":"s20","key":"pone.0279991.ref011","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/S1470-0328(03)00021-1","article-title":"Classification and heterogeneity of preterm birth.","volume":"110","author":"J-M Moutquin","year":"2003","journal-title":"BJOG: An International Journal of Obstetrics and Gynaecology."},{"key":"pone.0279991.ref012","doi-asserted-by":"crossref","first-page":"S136","DOI":"10.1016\/j.placenta.2011.01.003","article-title":"Review: A high capacity of the human placenta for genetic and epigenetic variation: Implications for assessing pregnancy outcome","volume":"32","author":"RKC Yuen","year":"2011","journal-title":"Placenta"},{"key":"pone.0279991.ref013","article-title":"The untapped potential of placenta-enriched molecules for diagnostic and therapeutic development","author":"C-AA Whigham","year":"2019","journal-title":"Placenta"},{"key":"pone.0279991.ref014","first-page":"1","article-title":"Proteomic signatures predict preeclampsia in individual cohorts but not across cohorts\u2013implications for clinical biomarker studies.","author":"MS Ghaemi","year":"2021","journal-title":"J Maternal-fetal Neonatal Medicine."},{"key":"pone.0279991.ref015","first-page":"83","article-title":"Clinical Prediction Models, A Practical Approach to Development, Validation, and Updating.","author":"EW Steyerberg","year":"2008","journal-title":"Statistics Biology Heal."},{"issue":"11","key":"pone.0279991.ref016","doi-asserted-by":"crossref","first-page":"e0225062","DOI":"10.1371\/journal.pone.0225062","article-title":"Unique transcriptomic landscapes identified in idiopathic spontaneous and infection related preterm births compared to normal term births.","volume":"14","author":"HM Brockway","year":"2019","journal-title":"PloS one"},{"issue":"9","key":"pone.0279991.ref017","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1038\/ejhg.2010.63","article-title":"DNA methylation profiling of human placentas reveals promoter hypomethylation of multiple genes in early-onset preeclampsia.","volume":"18","author":"RK Yuen","year":"2010","journal-title":"European journal of human genetics: EJHG."},{"issue":"9","key":"pone.0279991.ref018","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1080\/15592294.2015.1062964","article-title":"DNA methylation provides insight into intergenerational risk for preterm birth in African Americans.","volume":"10","author":"SE Parets","year":"2015","journal-title":"Epigenetics"},{"issue":"12","key":"pone.0279991.ref019","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1016\/j.placenta.2010.09.011","article-title":"Evaluating DNA methylation and gene expression variability in the human term placenta","volume":"31","author":"L Avila","year":"2010","journal-title":"Placenta"},{"issue":"1","key":"pone.0279991.ref020","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/hmg\/ddx391","article-title":"Mining DNA methylation alterations towards a classification of placental pathologies","volume":"27","author":"SL Wilson","year":"2018","journal-title":"Human molecular genetics"},{"issue":"2","key":"pone.0279991.ref021","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/0022-2836(87)90689-9","article-title":"CpG Islands in vertebrate genomes","volume":"196","author":"M Gardiner-Garden","year":"1987","journal-title":"J Mol Biol"},{"key":"pone.0279991.ref022","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.12688\/f1000research.8839.2","article-title":"A cross-package Bioconductor workflow for analysing methylation array data.","volume":"5","author":"J Maksimovic","year":"2016","journal-title":"F1000Research."},{"issue":"2","key":"pone.0279991.ref023","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nmeth.3252","article-title":"Orchestrating high-throughput genomic analysis with Bioconductor.","volume":"12","author":"W Huber","year":"2015","journal-title":"Nat Methods."},{"key":"pone.0279991.ref024","unstructured":"Team Rs. RStudio: Integrated Development for R. RStudio. 2020; Available from: http:\/\/www.rstudio.com\/"},{"key":"pone.0279991.ref025","unstructured":"Team RC. R: A language and environment for statistical ## computing. R Foundation for Statistical Computing [Internet]. 2020; Available from: https:\/\/www.R-project.org\/"},{"issue":"10","key":"pone.0279991.ref026","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1093\/bioinformatics\/btu049","article-title":"Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays","volume":"30","author":"MJ Aryee","year":"2014","journal-title":"Bioinformatics"},{"key":"pone.0279991.ref027","unstructured":"S D, P D, S B, Triche, T Jr, M B. methylumi: Handle Illumina methylation data. 2020; Available from: https:\/\/www.bioconductor.org\/packages\/release\/bioc\/html\/methylumi.html"},{"issue":"11","key":"pone.0279991.ref028","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1186\/s13059-014-0503-2","article-title":"Functional normalization of 450k methylation array data improves replication in large cancer studies","volume":"15","author":"J-P Fortin","year":"2014","journal-title":"Genome Biology"},{"issue":"4","key":"pone.0279991.ref029","first-page":"e22","article-title":"Comprehensive characterization, annotation and innovative use of Infinium DNA methylation BeadChip probes","volume":"45","author":"W Zhou","year":"2017","journal-title":"Nucleic Acids Research"},{"key":"pone.0279991.ref030","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.gdata.2016.05.012","article-title":"Identification of polymorphic and off-target probe binding sites on the Illumina Infinium MethylationEPIC BeadChip","volume":"9","author":"DL McCartney","year":"2016","journal-title":"Genomics Data"},{"issue":"1","key":"pone.0279991.ref031","doi-asserted-by":"crossref","first-page":"9354","DOI":"10.1038\/s41598-019-45839-z","article-title":"The ENCODE Blacklist: Identification of Problematic Regions of the Genome.","volume":"9","author":"HM Amemiya","year":"2019","journal-title":"Scientific Reports"},{"key":"pone.0279991.ref032","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3389\/fgene.2018.00083","article-title":"Adjusting for Batch Effects in DNA Methylation Microarray Data, a Lesson Learned.","volume":"9","author":"EM Price","year":"2018","journal-title":"Frontiers in genetics."},{"issue":"1","key":"pone.0279991.ref033","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1186\/1471-2105-11-587","article-title":"Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis","volume":"11","author":"P Du","year":"2010","journal-title":"BMC Bioinformatics"},{"issue":"7","key":"pone.0279991.ref034","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"ME Ritchie","year":"2015","journal-title":"Nucleic Acids Research"},{"issue":"1","key":"pone.0279991.ref035","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":"Y Benjamini","year":"1995","journal-title":"Journal of the Royal Statistical Society: Series B (Methodological)."},{"key":"pone.0279991.ref036","unstructured":"Oliveros, J.C. Venny. An interactive tool for comparing lists with Venn\u2019s diagrams. 2015; Available from: https:\/\/bioinfogp.cnb.csic.es\/tools\/venny\/index.html"},{"issue":"1","key":"pone.0279991.ref037","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1756-8935-8-6","article-title":"De novo identification of differentially methylated regions in the human genome.","volume":"8","author":"TJ Peters","year":"2015","journal-title":"Epigenetics & Chromatin."},{"issue":"D1","key":"pone.0279991.ref038","doi-asserted-by":"crossref","first-page":"D183","DOI":"10.1093\/nar\/gkw1138","article-title":"PANTHER version 11: expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements","volume":"45","author":"H Mi","year":"2017","journal-title":"Nucleic Acids Research"},{"issue":"1","key":"pone.0279991.ref039","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/s12859-015-0641-x","article-title":"An evaluation of statistical methods for DNA methylation microarray data analysis","volume":"16","author":"D Li","year":"2015","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"pone.0279991.ref040","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1186\/s12864-019-5761-7","article-title":"Guidance for DNA methylation studies: statistical insights from the Illumina EPIC array","volume":"20","author":"G Mansell","year":"2019","journal-title":"Bmc Genomics"},{"issue":"1","key":"pone.0279991.ref041","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13148-019-0630-4","article-title":"Differences in expression rather than methylation at placenta-specific imprinted loci is associated with intrauterine growth restriction.","volume":"11","author":"A Monteagudo-S\u00e1nchez","year":"2019","journal-title":"Clin Epigenetics"},{"issue":"Suppl 1","key":"pone.0279991.ref042","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1016\/j.placenta.2017.12.013","article-title":"Utility of DNA methylation to assess placental health","volume":"64","author":"SL Wilson","year":"2018","journal-title":"Placenta"},{"issue":"1","key":"pone.0279991.ref043","first-page":"138","article-title":"DNA hypomethylation and human diseases","volume":"1775","author":"AS Wilson","year":"2007","journal-title":"Biochimica Et Biophysica Acta Bba\u2014Rev Cancer"},{"issue":"12","key":"pone.0279991.ref044","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15592294.2019.1638701","article-title":"DNA hypermethylation in disease: mechanisms and clinical relevance","volume":"14","author":"M. Ehrlich","year":"2019","journal-title":"Epigenetics"},{"issue":"1","key":"pone.0279991.ref045","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1128\/MCB.26.1.169-181.2006","article-title":"A Family of Human Zinc Finger Proteins That Bind Methylated DNA and Repress Transcription","volume":"26","author":"GJP Filion","year":"2006","journal-title":"Mol Cell Biol"},{"key":"pone.0279991.ref046","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.biopha.2018.01.132","article-title":"Tumor suppressive ZBTB4 inhibits cell growth by regulating cell cycle progression and apoptosis in Ewing sarcoma","volume":"100","author":"Y Yu","year":"2018","journal-title":"Biomed Pharmacother"},{"issue":"11","key":"pone.0279991.ref047","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1038\/emboj.2008.85","article-title":"Zbtb4 represses transcription of P21CIP1 and controls the cellular response to p53 activation","volume":"27","author":"A Weber","year":"2008","journal-title":"Embo J"},{"issue":"1","key":"pone.0279991.ref048","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1093\/biolre\/iox163","article-title":"Comparative transcriptomic analysis of human placentae at term and preterm delivery","volume":"98","author":"AG Paquette","year":"2018","journal-title":"Biology of reproduction"},{"issue":"3","key":"pone.0279991.ref049","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1172\/JCI40051","article-title":"Uterine-specific p53 deficiency confers premature uterine senescence and promotes preterm birth in mice","volume":"120","author":"Y Hirota","year":"2010","journal-title":"Journal of Clinical Investigation"},{"issue":"31","key":"pone.0279991.ref050","doi-asserted-by":"crossref","first-page":"28271","DOI":"10.1074\/jbc.M204929200","article-title":"Amisyn, a Novel Syntaxin-binding Protein That May Regulate SNARE Complex Assembly*","volume":"277","author":"SJ Scales","year":"2002","journal-title":"J Biol Chem"},{"issue":"12","key":"pone.0279991.ref051","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1111\/tra.12524","article-title":"SNARE proteins in membrane trafficking","volume":"18","author":"T Wang","year":"2017","journal-title":"Traffic"},{"key":"pone.0279991.ref052","first-page":"5","article-title":"The Multifaceted Role of SNARE Proteins in Membrane Fusion.","volume":"8","author":"J Han","year":"2017","journal-title":"Front Physiol"},{"issue":"4","key":"pone.0279991.ref053","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1093\/jmcb\/mjr004","article-title":"Counting the SNAREs needed for membrane fusion.","volume":"3","author":"G van den Bogaart","year":"2011","journal-title":"J Mol Cell Biol"},{"key":"pone.0279991.ref054","doi-asserted-by":"crossref","first-page":"e41711","DOI":"10.7554\/eLife.41711","article-title":"Fusion pore regulation by cAMP\/Epac2 controls cargo release during insulin exocytosis.","volume":"8","author":"A Gu\u010dek","year":"2019","journal-title":"Elife"},{"issue":"1","key":"pone.0279991.ref055","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/1471-2199-7-39","article-title":"Specific use of start codons and cellular localization of splice variants of human phosphodiesterase 9A gene","volume":"7","author":"C Rentero","year":"2006","journal-title":"Bmc Mol Biol"},{"key":"pone.0279991.ref056","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3389\/fphar.2015.00202","article-title":"Spatiotemporal regulation of cAMP signaling controls the human trophoblast fusion.","volume":"6","author":"P Gerbaud","year":"2015","journal-title":"Front Pharmacol"},{"issue":"11","key":"pone.0279991.ref057","doi-asserted-by":"crossref","first-page":"e27709","DOI":"10.1371\/journal.pone.0027709","article-title":"Non-Invasive Epigenetic Detection of Fetal Trisomy 21 in First Trimester Maternal Plasma.","volume":"6","author":"JH Lim","year":"2011","journal-title":"Plos One."},{"issue":"10","key":"pone.0279991.ref058","first-page":"3700","article-title":"Defect of villous cytotrophoblast differentiation into syncytiotrophoblast in Down\u2019s syndrome","volume":"85","author":"JL Frendo","year":"2000","journal-title":"The Journal of clinical endocrinology and metabolism"},{"key":"pone.0279991.ref059","doi-asserted-by":"crossref","first-page":"S81","DOI":"10.1016\/j.placenta.2011.11.007","article-title":"Review: Human trophoblast fusion and differentiation: Lessons from trisomy 21 placenta","volume":"33","author":"G Pidoux","year":"2011","journal-title":"Placenta"},{"issue":"2\u20133","key":"pone.0279991.ref060","first-page":"475","article-title":"Trisomy 21- affected placentas highlight prerequisite factors for human trophoblast fusion and differentiation","volume":"54","author":"A Malassin\u00e9","year":"2009","journal-title":"International Journal of Developmental Biology"},{"key":"pone.0279991.ref061","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.placenta.2017.07.017","article-title":"Expression and function of NOD-like receptors by human term gestation-associated tissues","volume":"58","author":"AH Bryant","year":"2017","journal-title":"Placenta"},{"issue":"1","key":"pone.0279991.ref062","doi-asserted-by":"crossref","DOI":"10.1095\/biolreprod.113.110056","article-title":"NOD1 and NOD2 Regulate Proinflammatory and Prolabor Mediators in Human Fetal Membranes and Myometrium via Nuclear Factor-Kappa B","volume":"89","author":"M. Lappas","year":"2013","journal-title":"Biol Reprod"},{"issue":"6","key":"pone.0279991.ref063","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1042\/BST0351479","article-title":"Nod1 and Nod2 in innate immunity and human inflammatory disorders","volume":"35","author":"LL Bourhis","year":"2007","journal-title":"Biochem Soc T"},{"issue":"6","key":"pone.0279991.ref064","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1095\/biolreprod.110.086413","article-title":"Transcriptomic Signature of Trophoblast Differentiation in a Human Embryonic Stem Cell Model","volume":"84","author":"M Marchand","year":"2011","journal-title":"Biology of Reproduction"},{"issue":"2","key":"pone.0279991.ref065","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1210\/me.2012-1309","article-title":"Glucocorticoid Receptor Signaling Contributes to Constitutive Activation of the Noncanonical NF-\u03baB Pathway in Term Human Placenta","volume":"27","author":"B Wang","year":"2013","journal-title":"Molecular Endocrinology"},{"issue":"1","key":"pone.0279991.ref066","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/j.1600-065X.2012.01146.x","article-title":"PAMPs and DAMPs: signal 0s that spur autophagy and immunity","volume":"249","author":"D Tang","year":"2012","journal-title":"Immunological Reviews"},{"issue":"4","key":"pone.0279991.ref067","doi-asserted-by":"crossref","first-page":"e1865","DOI":"10.1371\/journal.pone.0001865","article-title":"Maternal TLR4 and NOD2 Gene Variants, Pro-Inflammatory Phenotype and Susceptibility to Early-Onset Preeclampsia and HELLP Syndrome.","volume":"3","author":"BB van Rijn","year":"2008","journal-title":"Plos One."},{"issue":"4","key":"pone.0279991.ref068","doi-asserted-by":"crossref","first-page":"e1121","DOI":"10.1002\/cti2.1121","article-title":"Targeting Toll\u2010like receptor\u20104 to tackle preterm birth and fetal inflammatory injury.","volume":"9","author":"SA Robertson","year":"2020","journal-title":"Clin Transl Immunol"},{"issue":"1","key":"pone.0279991.ref069","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.1600-0897.2006.00447.x","article-title":"NOD Protein Expression and Function in First Trimester Trophoblast Cells","volume":"57","author":"MJ Costello","year":"2007","journal-title":"Am J Reprod Immunol"},{"issue":"3","key":"pone.0279991.ref070","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.ajog.2017.12.009","article-title":"Spontaneous preterm birth: advances toward the discovery of genetic predisposition.","volume":"218","author":"JF Strauss","year":"2018","journal-title":"Am J Obstet Gynecol"},{"issue":"12","key":"pone.0279991.ref071","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1093\/molehr\/gah120","article-title":"Polymorphisms of genes involved in innate immunity: association with preterm delivery","volume":"10","author":"H\u00e4rtel Ch","year":"2004","journal-title":"Mhr Basic Sci Reproductive Medicine"},{"issue":"1","key":"pone.0279991.ref072","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s13148-020-00873-x","article-title":"DNA methylation loci in placenta associated with birthweight and expression of genes relevant for early development and adult diseases","volume":"12","author":"F Tekola-Ayele","year":"2020","journal-title":"Clin Epigenetics"},{"key":"pone.0279991.ref073","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.preghy.2019.12.007","article-title":"Meta-analysis of gene expression profiles in preeclampsia","volume":"19","author":"KE Vennou","year":"2020","journal-title":"Pregnancy Hypertens"},{"key":"pone.0279991.ref074","doi-asserted-by":"crossref","first-page":"100856","DOI":"10.1016\/j.mgene.2021.100856","article-title":"Association between GCK gene polymorphism and gestational diabetes mellitus and its pregnancy outcomes","volume":"28","author":"R Ramasammy","year":"2021","journal-title":"Meta Gene"},{"issue":"4","key":"pone.0279991.ref075","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1093\/hmg\/ddx429","article-title":"Genome wide association study of offspring birth weight in 86577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics","volume":"27","author":"RN Beaumont","year":"2018","journal-title":"Human Molecular Genetics"},{"issue":"8","key":"pone.0279991.ref076","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.placenta.2009.05.008","article-title":"Placental Dysferlin Expression is Reduced in Severe Preeclampsia","volume":"30","author":"CT Lang","year":"2009","journal-title":"Placenta"},{"issue":"4","key":"pone.0279991.ref077","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s00109-005-0032-2","article-title":"The importance of cysteine cathepsin proteases for placental development","volume":"84","author":"A Varanou","year":"2006","journal-title":"J Mol Med"},{"issue":"1","key":"pone.0279991.ref078","first-page":"133","article-title":"Screening for differential methylation status in human placenta in preeclampsia using a CpG island plus promoter microarray","volume":"30","author":"R-Z Jia","year":"2012","journal-title":"Int J Mol Med"},{"issue":"6220","key":"pone.0279991.ref079","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Tissue-based map of the human proteome","volume":"347","author":"M Uhl\u00e9n","year":"2015","journal-title":"Science"},{"issue":"1\u20132","key":"pone.0279991.ref080","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.cellimm.2012.07.009","article-title":"VSTM1-v2, a novel soluble glycoprotein, promotes the differentiation and activation of Th17 cells","volume":"278","author":"X Guo","year":"2012","journal-title":"Cell Immunol"},{"issue":"10","key":"pone.0279991.ref081","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.placenta.2010.07.011","article-title":"Wnt Signalling in Implantation, Decidualisation and Placental Differentiation\u2013Review","volume":"31","author":"S Sonderegger","year":"2010","journal-title":"Placenta"},{"key":"pone.0279991.ref082","doi-asserted-by":"crossref","first-page":"190","DOI":"10.3389\/fgene.2013.00190","article-title":"Human placental trophoblast invasion and differentiation: a particular focus on Wnt signaling","volume":"4","author":"M Kn\u00f6fler","year":"2013","journal-title":"Frontiers in Genetics"},{"issue":"9","key":"pone.0279991.ref083","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.placenta.2010.06.017","article-title":"Cadherins in the human placenta\u2013epithelial\u2013mesenchymal transition (EMT) and placental development.","volume":"31","author":"MI Kokkinos","year":"2010","journal-title":"Placenta"},{"issue":"2","key":"pone.0279991.ref084","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s43032-020-00364-7","article-title":"The Involvement of Cell Adhesion Molecules, Tight Junctions, and Gap Junctions in Human Placentation.","volume":"28","author":"EA Adu-Gyamfi","year":"2021","journal-title":"Reprod Sci."},{"issue":"10","key":"pone.0279991.ref085","doi-asserted-by":"crossref","first-page":"H1295","DOI":"10.1152\/ajpheart.00958.2015","article-title":"DNA methylation profiles in preeclampsia and healthy control placentas","volume":"310","author":"KR Yeung","year":"2016","journal-title":"Am J Physiol-heart C"},{"issue":"18","key":"pone.0279991.ref086","doi-asserted-by":"crossref","first-page":"e100849","DOI":"10.15252\/embj.2018100849","article-title":"Molecular pathways of senescence regulate placental structure and function","volume":"38","author":"H Gal","year":"2019","journal-title":"Embo J"},{"issue":"1","key":"pone.0279991.ref087","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1186\/1471-2148-13-247","article-title":"ANRIL\/CDKN2B-AS shows two-stage clade-specific evolution and becomes conserved after transposon insertions in simians","volume":"13","author":"S He","year":"2013","journal-title":"Bmc Evol Biol"},{"issue":"12","key":"pone.0279991.ref088","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1080\/15592294.2018.1549462","article-title":"The role of DNA methylation in human trophoblast differentiation","volume":"13","author":"T Gamage","year":"2018","journal-title":"Epigenetics"},{"issue":"3","key":"pone.0279991.ref089","doi-asserted-by":"crossref","first-page":"279","DOI":"10.2217\/epi-2016-0103","article-title":"Accelerated placental aging in early onset preeclampsia pregnancies identified by DNA methylation","volume":"9","author":"BT Mayne","year":"2016","journal-title":"Epigenomics-uk"},{"issue":"17","key":"pone.0279991.ref090","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1177\/1535370220918329","article-title":"Current perspectives on the cellular and molecular features of epigenetic ageing","volume":"245","author":"K Raj","year":"2020","journal-title":"Exp Biol Med"},{"issue":"12","key":"pone.0279991.ref091","doi-asserted-by":"crossref","first-page":"4238","DOI":"10.18632\/aging.102049","article-title":"Placental epigenetic clocks: estimating gestational age using placental DNA methylation levels","volume":"11","author":"Y Lee","year":"2019","journal-title":"Aging"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0279991","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T22:50:25Z","timestamp":1729119025000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0279991"}},"subtitle":[],"editor":[{"given":"Christopher","family":"Torrens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,3,23]]},"references-count":91,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0279991","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,23]]}}}