{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T03:23:04Z","timestamp":1782962584068,"version":"3.54.5"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T00:00:00Z","timestamp":1565740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD954931"],"award-info":[{"award-number":["HD954931"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Imperial NIHR Biomedical Research Centre"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,21]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Preterm labor (PTL) is the predominant cause of childhood morbidity and mortality. It has several phenotypes, each with a distinct etiology often involving inflammation. Here, in samples of reproductive tissues obtained in early PTL from women with phenotypically defined PTL, we examined the presence and distribution of inflammation and its relationship with prolabor gene expression. In chorioamnionitis (CA-PTL), cytokine protein concentrations were increased across all tissues; in idiopathic (I-PTL), the inflammatory changes were limited to the choriodecidua; inflammation was not a feature of placental abruption (PA-PTL). CA-PTL was associated with activation of p65 in the myometrium and AP-1 in the choriodecidua, and PA-PTL with CREB in the choriodecidua. In the myometrium, PGHS-2 mRNA level was increased in CA- and I-PTL; in the amnion, PGHS-2 mRNA level was higher in PA- and I-PTL, while in CA-PTL, OT, OTR mRNA, and CX-43 expression were increased. In the choriodecidua, PGHS-2 mRNA level was unchanged, but in CA and I-PTL, OT mRNA level were increased and OTR was reduced. These data show that CA-PTL is associated with widespread inflammation and prolabor gene expression. In contrast, in I-PTL, inflammation is limited to the choriodecidua, with discrete increases in PGHS-2 in the amnion and OT in the choriodecidua. Inflammation is not a feature of PA-PTL, which is associated with increased OT and OTR in the amnion.<\/jats:p>","DOI":"10.1093\/biolre\/ioz144","type":"journal-article","created":{"date-parts":[[2019,8,15]],"date-time":"2019-08-15T02:26:51Z","timestamp":1565836011000},"page":"1031-1045","source":"Crossref","is-referenced-by-count":14,"title":["Distinct preterm labor phenotypes have unique inflammatory signatures and contraction associated protein profiles\u2020"],"prefix":"10.1093","volume":"101","author":[{"given":"Natasha","family":"Singh","sequence":"first","affiliation":[{"name":"Chelsea and Westminster Hospital, London, United Kingdom"},{"name":"Institute of Reproductive and Developmental Biology, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bronwen","family":"Herbert","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Developmental Biology, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Sooranna","sequence":"additional","affiliation":[{"name":"Chelsea and Westminster Hospital, London, United Kingdom"},{"name":"Institute of Reproductive and Developmental Biology, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anya","family":"Das","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Developmental Biology, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suren R","family":"Sooranna","sequence":"additional","affiliation":[{"name":"Chelsea and Westminster Hospital, London, United Kingdom"},{"name":"Institute of Reproductive and Developmental Biology, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M","family":"Yellon","sequence":"additional","affiliation":[{"name":"Longo Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R","family":"Johnson","sequence":"additional","affiliation":[{"name":"Chelsea and Westminster Hospital, London, United Kingdom"},{"name":"Institute of Reproductive and Developmental Biology, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,8,14]]},"reference":[{"issue":"9832","key":"2019112601003158200_ref1","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1016\/S0140-6736(12)60560-1","article-title":"Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000","volume":"379","author":"Liu","year":"2012","journal-title":"Lancet"},{"issue":"9606","key":"2019112601003158200_ref2","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0140-6736(08)60074-4","article-title":"Epidemiology and causes of preterm birth","volume":"371","author":"Goldenberg","year":"2008","journal-title":"Lancet"},{"issue":"6198","key":"2019112601003158200_ref3","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1126\/science.1251816","article-title":"Preterm labor: one syndrome, many causes","volume":"345","author":"Romero","year":"2014","journal-title":"Science"},{"issue":"5","key":"2019112601003158200_ref4","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1111\/aji.12296","article-title":"Prevalence and clinical significance of sterile intra-amniotic inflammation in patients with preterm labor and intact membranes","volume":"72","author":"Romero","year":"2014","journal-title":"Am J Reprod Immunol"},{"key":"2019112601003158200_ref5","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1111\/j.1749-6632.1994.tb21771.x","article-title":"The preterm labor syndrome","volume":"734","author":"Romero","year":"1994","journal-title":"Ann N Y Acad Sci"},{"issue":"3","key":"2019112601003158200_ref6","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1097\/00003081-198809000-00006","article-title":"Infection and preterm labor","volume":"31","author":"Romero","year":"1988","journal-title":"Clin Obstet Gynecol"},{"key":"2019112601003158200_ref7","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1053\/plac.2002.0948","article-title":"Cytokines, prostaglandins and parturition\u2014a review","volume":"24","author":"Keelan","year":"2003","journal-title":"Placenta"},{"issue":"6","key":"2019112601003158200_ref8","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1515\/JPM.2001.072","article-title":"Tissue concentrations of cytokines in the lower uterine segment during preterm parturition","volume":"29","author":"Winkler","year":"2001","journal-title":"J Perinat Med"},{"issue":"Suppl 20","key":"2019112601003158200_ref9","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1046\/j.1471-0528.2003.00062.x","article-title":"Role of cytokines and other inflammatory mediators","volume":"110","author":"Winkler","year":"2003","journal-title":"BJOG"},{"issue":"5","key":"2019112601003158200_ref10","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1095\/biolreprod.109.080432","article-title":"The role of chemokines in term and premature rupture of the fetal membranes: a review","volume":"82","author":"Gomez-Lopez","year":"2010","journal-title":"Biol Reprod"},{"issue":"8","key":"2019112601003158200_ref11","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.placenta.2005.08.009","article-title":"The placenta cytokine network and inflammatory signals","volume":"27","author":"Hauguel-de Mouzon","year":"2006","journal-title":"Placenta"},{"issue":"2","key":"2019112601003158200_ref12","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1095\/biolreprod.111.095505","article-title":"Macrophages infiltrate the human and rat decidua during term and preterm labor: evidence that decidual inflammation precedes labor","volume":"86","author":"Hamilton","year":"2012","journal-title":"Biol Reprod"},{"issue":"2","key":"2019112601003158200_ref13","doi-asserted-by":"crossref","first-page":"e56946","DOI":"10.1371\/journal.pone.0056946","article-title":"Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour","volume":"8","author":"Hamilton","year":"2013","journal-title":"PLoS One"},{"issue":"Suppl 2","key":"2019112601003158200_ref14","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1080\/14767050902860690","article-title":"The preterm parturition syndrome and its implications for understanding the biology, risk assessment, diagnosis, treatment and prevention of preterm birth","volume":"22","author":"Gotsch","year":"2009","journal-title":"J Matern Fetal Neonatal Med"},{"key":"2019112601003158200_ref15","doi-asserted-by":"crossref","first-page":"e13049","DOI":"10.1111\/aji.13049","article-title":"Inflammasome activation during spontaneous preterm labor with intra-amniotic infection or sterile intra-amniotic inflammation","author":"Gomez-Lopez","year":"2018","journal-title":"Am J Reprod Immunol"},{"issue":"6","key":"2019112601003158200_ref16","doi-asserted-by":"crossref","first-page":"830 e1","DOI":"10.1016\/j.ajog.2015.08.028","article-title":"Uterine overdistention induces preterm labor mediated by inflammation: observations in pregnant women and nonhuman primates","volume":"213","author":"Adams Waldorf","year":"2015","journal-title":"Am J Obstet Gynecol"},{"issue":"5","key":"2019112601003158200_ref17","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.siny.2006.02.011","article-title":"Inflammatory responses in the placenta and umbilical cord","volume":"11","author":"Redline","year":"2006","journal-title":"Semin Fetal Neonatal Med"},{"issue":"4 Suppl","key":"2019112601003158200_ref18","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1016\/j.ajog.2015.08.041","article-title":"Chronic inflammation of the placenta: definition, classification, pathogenesis, and clinical significance","volume":"213","author":"Kim","year":"2015","journal-title":"Am J Obstet Gynecol"},{"key":"2019112601003158200_ref19","doi-asserted-by":"crossref","DOI":"10.1530\/JOE-17-0318","article-title":"Is myometrial inflammation a cause or a consequence of term human labour?","author":"Singh","year":"2017","journal-title":"The Journal of Endocrinology"},{"issue":"12","key":"2019112601003158200_ref20","doi-asserted-by":"crossref","first-page":"e79941","DOI":"10.1371\/journal.pone.0079941","article-title":"Acute histologic chorioamnionitis is a risk factor for adverse neonatal outcome in late preterm birth after preterm premature rupture of membranes","volume":"8","author":"Lee","year":"2013","journal-title":"PLoS One"},{"issue":"3","key":"2019112601003158200_ref21","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.ajog.2006.05.049","article-title":"Placental inflammation and viral infection are implicated in second trimester pregnancy loss","volume":"195","author":"Srinivas","year":"2006","journal-title":"Am J Obstet Gynecol"},{"issue":"5","key":"2019112601003158200_ref22","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1080\/15513819609169300","article-title":"Clinical significance of increasing histologic severity of acute inflammation in the fetal membranes and umbilical cord","volume":"16","author":"Hoeven","year":"1996","journal-title":"Pediatr Pathol Lab Med"},{"key":"2019112601003158200_ref23","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/1477-7827-7-117","article-title":"Tissue-specific cytokine release from human extra-placental membranes stimulated by lipopolysaccharide in a two-compartment tissue culture system","volume":"7","author":"Thiex","year":"2009","journal-title":"Reprod Biol Endocrinol"},{"key":"2019112601003158200_ref24","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.placenta.2016.06.005","article-title":"Human amnion mesenchymal cells are pro-inflammatory when activated by the toll-like receptor 2\/6 ligand, macrophage-activating lipoprotein-2","volume":"44","author":"Sato","year":"2016","journal-title":"Placenta"},{"issue":"7","key":"2019112601003158200_ref25","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1182\/blood.V76.7.1392.1392","article-title":"Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocytes","volume":"76","author":"Velde","year":"1990","journal-title":"Blood"},{"issue":"13","key":"2019112601003158200_ref26","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.3109\/14767058.2013.857397","article-title":"Tissue-specific IL-10 secretion profile from term human fetal membranes stimulated with pathogenic microorganisms associated with preterm labor in a two-compartment tissue culture system","volume":"27","author":"Zaga-Clavellina","year":"2014","journal-title":"J Matern Fetal Neonatal Med"},{"issue":"14","key":"2019112601003158200_ref27","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.3109\/14767058.2013.784258","article-title":"Soluble ST2 in the fetal inflammatory response syndrome: in vivo evidence of activation of the anti-inflammatory limb of the immune response","volume":"26","author":"Stampalija","year":"2013","journal-title":"J Matern Fetal Neonatal Med"},{"issue":"3","key":"2019112601003158200_ref28","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1210\/en.2010-1105","article-title":"The molecular mechanisms of cervical ripening differ between term and preterm birth","volume":"152","author":"Holt","year":"2011","journal-title":"Endocrinology"},{"issue":"4","key":"2019112601003158200_ref29","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.aah4576","article-title":"Group B Streptococcus circumvents neutrophils and neutrophil extracellular traps during amniotic cavity invasion and preterm labor","volume":"1","author":"Boldenow","year":"2016","journal-title":"Sci Immunol"},{"issue":"10","key":"2019112601003158200_ref30","first-page":"22","article-title":"NFkappaB and AP-1 drive human myometrial IL8 expression","volume":"504952","author":"Khanjani","year":"2012","journal-title":"Mediat Inflamm"},{"issue":"3","key":"2019112601003158200_ref31","doi-asserted-by":"crossref","first-page":"480","DOI":"10.3346\/jkms.2017.32.3.480","article-title":"Amniotic fluid infection, cytokine levels, and mortality and adverse pulmonary, intestinal, and neurologic outcomes in infants at 32 weeks' gestation or less","volume":"32","author":"Jung","year":"2017","journal-title":"J Korean Med Sci"},{"issue":"4","key":"2019112601003158200_ref32","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1540\/jsmr.31.175","article-title":"The regulation of oxytocin receptor expression in human myometrial monolayer culture","volume":"31","author":"Adachi","year":"1995","journal-title":"J Smooth Muscle Res"},{"issue":"1","key":"2019112601003158200_ref33","doi-asserted-by":"crossref","first-page":"21S","DOI":"10.1042\/bst023021s","article-title":"Second messenger pathways for oxytocin and prostaglandins in human myometrium","volume":"23","author":"Phaneuf","year":"1995","journal-title":"Biochem Soc Trans"},{"issue":"4 Pt 1","key":"2019112601003158200_ref34","first-page":"E634","article-title":"ERK2 mediates oxytocin-stimulated PGE2 synthesis","volume":"274","author":"Strakova","year":"1998","journal-title":"Am J Phys"},{"issue":"2","key":"2019112601003158200_ref35","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/0301-2115(95)02200-Q","article-title":"Maternal levels of serum-soluble CD8 and IL-2R are not significantly elevated in idiopathic preterm labour","volume":"62","author":"Divers","year":"1995","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"2019112601003158200_ref36","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/1477-7827-3-39","article-title":"Non-infected preterm parturition is related to increased concentrations of IL-6, IL-8 and MCP-1 in human cervix","volume":"3","author":"Tornblom","year":"2005","journal-title":"Reprod Biol Endocrinol"},{"issue":"5","key":"2019112601003158200_ref37","doi-asserted-by":"crossref","first-page":"592 e1","DOI":"10.1016\/j.ajog.2017.08.008","article-title":"Preterm labor in the absence of acute histologic chorioamnionitis is characterized by cellular senescence of the chorioamniotic membranes","volume":"217","author":"Gomez-Lopez","year":"2017","journal-title":"Am J Obstet Gynecol"},{"issue":"2","key":"2019112601003158200_ref38","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1309\/KC6KDTX98LFYB3J7","article-title":"Myometrial inflammation in human delivery and its association with labor and infection","volume":"120","author":"Keski-Nisula","year":"2003","journal-title":"Am J Clin Pathol"},{"issue":"1\u20132","key":"2019112601003158200_ref39","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ejogrb.2006.01.016","article-title":"Evidence of placental abruption as a chronic process: associations with vaginal bleeding early in pregnancy and placental lesions","volume":"128","author":"Ananth","year":"2006","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"issue":"3","key":"2019112601003158200_ref40","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.ajog.2007.06.012","article-title":"Histologic evidence of inflammation and risk of placental abruption","volume":"197","author":"Nath","year":"2007","journal-title":"Am J Obstet Gynecol"},{"issue":"11","key":"2019112601003158200_ref41","doi-asserted-by":"crossref","first-page":"4411","DOI":"10.1210\/en.2016-1514","article-title":"Cyclic AMP effectors regulate myometrial oxytocin receptor expression","volume":"157","author":"Yulia","year":"2016","journal-title":"Endocrinology"},{"issue":"1","key":"2019112601003158200_ref42","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1677\/joe.0.1610143","article-title":"Oxytocin receptor expression in human term and preterm gestational tissues prior to and following the onset of labour","volume":"161","author":"Wathes","year":"1999","journal-title":"J Endocrinol"},{"issue":"5","key":"2019112601003158200_ref43","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1096\/fj.13-247783","article-title":"Activator protein 1 is a key terminal mediator of inflammation-induced preterm labor in mice","volume":"28","author":"MacIntyre","year":"2014","journal-title":"FASEB J"}],"container-title":["Biology of Reproduction"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/biolreprod\/advance-article-pdf\/doi\/10.1093\/biolre\/ioz144\/30126565\/ioz144.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/biolreprod\/article-pdf\/101\/5\/1031\/31137914\/ioz144.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/biolreprod\/article-pdf\/101\/5\/1031\/31137914\/ioz144.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T18:02:32Z","timestamp":1664128952000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biolreprod\/article\/101\/5\/1031\/5549645"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,14]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,8,14]]},"published-print":{"date-parts":[[2019,11,21]]}},"URL":"https:\/\/doi.org\/10.1093\/biolre\/ioz144","relation":{},"ISSN":["0006-3363","1529-7268"],"issn-type":[{"value":"0006-3363","type":"print"},{"value":"1529-7268","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,11]]},"published":{"date-parts":[[2019,8,14]]}}}