{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:44:10Z","timestamp":1790646250478,"version":"4.1.0"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"22","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\/06778-2019"],"award-info":[{"award-number":["RGPIN\/06778-2019"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002146","name":"IFSA","doi-asserted-by":"publisher","award":["CZ.02.1.01\/0.0\/0.0\/16_019\/0000841"],"award-info":[{"award-number":["CZ.02.1.01\/0.0\/0.0\/16_019\/0000841"]}],"id":[{"id":"10.13039\/100002146","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007397","name":"Charles University","doi-asserted-by":"publisher","award":["SVV 2020\/260414"],"award-info":[{"award-number":["SVV 2020\/260414"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009553","name":"Czech Health Research Council","doi-asserted-by":"publisher","award":["NU20-01-00264"],"award-info":[{"award-number":["NU20-01-00264"]}],"id":[{"id":"10.13039\/501100009553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Spontaneous preterm birth is a serious medical condition responsible for substantial perinatal morbidity and mortality. Its phenotypic characteristics, preterm labor with intact membranes (PTL) and preterm premature rupture of the membranes (PPROM), are associated with significantly increased risks of neurological and behavioral alterations in childhood and later life. Recognizing the inflammatory milieu associated with PTL and PPROM, here, we examined expression signatures of placental tryptophan metabolism, an important pathway in prenatal brain development and immunotolerance. The study was performed in a well-characterized clinical cohort of healthy term pregnancies (n\u2009=\u200939) and 167 preterm deliveries (PTL, n\u2009=\u200938 and PPROM, n\u2009=\u2009129). Within the preterm group, we then investigated potential mechanistic links between differential placental tryptophan pathway expression, preterm birth and both intra-amniotic markers (such as amniotic fluid interleukin-6) and maternal inflammatory markers (such as maternal serum C-reactive protein and white blood cell count). We show that preterm birth is associated with significant changes in placental tryptophan metabolism. Multifactorial analysis revealed similarities in expression patterns associated with multiple phenotypes of preterm delivery. Subsequent correlation computations and mediation analyses identified links between intra-amniotic and maternal inflammatory markers and placental serotonin and kynurenine pathways of tryptophan catabolism. Collectively, the findings suggest that a hostile inflammatory environment associated with preterm delivery underlies the mechanisms affecting placental endocrine\/transport functions and may contribute to disruption of developmental programming of the fetal brain.<\/jats:p>","DOI":"10.1093\/hmg\/ddab169","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T19:11:04Z","timestamp":1624302664000},"page":"2053-2067","source":"Crossref","is-referenced-by-count":38,"title":["Prenatal inflammation as a link between placental expression signature of tryptophan metabolism and preterm birth"],"prefix":"10.1093","volume":"30","author":[{"given":"Rona","family":"Karahoda","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove 50005, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane","family":"Robles","sequence":"additional","affiliation":[{"name":"INRS-Centre Armand-Frappier Sant\u00e9 Biotechnologie, Laval, QC H7V 1B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Marushka","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University, Prague 50005, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslav","family":"Stranik","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital Hradec Kralove, Hradec Kralove 50005, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cilia","family":"Abad","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove 50005, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Horackova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove 50005, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurjen Duintjer","family":"Tebbens","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University, Prague 50005, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy","family":"Vaillancourt","sequence":"additional","affiliation":[{"name":"INRS-Centre Armand-Frappier Sant\u00e9 Biotechnologie, Laval, QC H7V 1B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Kacerovsky","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital Hradec Kralove, Hradec Kralove 50005, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6712-097X","authenticated-orcid":false,"given":"Frantisek","family":"Staud","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove 50005, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"2021110209350254700_ref1","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. 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Gynecol."},{"key":"2021110209350254700_ref5","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0140-6736(08)60136-1","article-title":"An overview of mortality and sequelae of preterm birth from infancy to adulthood","volume":"371","author":"Saigal","year":"2008","journal-title":"Lancet"},{"key":"2021110209350254700_ref6","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1001\/archgenpsychiatry.2011.1374","article-title":"Preterm birth and psychiatric disorders in young adult life","volume":"69","author":"Nosarti","year":"2012","journal-title":"Arch. Gen. Psychiatry"},{"key":"2021110209350254700_ref7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.biocel.2018.09.016","article-title":"Trophoblast: the central unit of fetal growth, protection and programming","volume":"105","author":"Staud","year":"2018","journal-title":"Int. J. Biochem. 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Psychiatry"},{"key":"2021110209350254700_ref10","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nature09972","article-title":"A transient placental source of serotonin for the fetal forebrain","volume":"472","author":"Bonnin","year":"2011","journal-title":"Nature"},{"key":"2021110209350254700_ref11","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.1600-079X.2008.00555.x","article-title":"Human placental trophoblasts synthesize melatonin and express its receptors","volume":"45","author":"Lanoix","year":"2008","journal-title":"J. Pineal Res."},{"key":"2021110209350254700_ref12","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3389\/fimmu.2014.00230","article-title":"The role of placental tryptophan catabolism","volume":"5","author":"Sedlmayr","year":"2014","journal-title":"Front. 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