{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:05:09Z","timestamp":1790690709454,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Excessive placental inflammation is associated with several pathological conditions, including stillbirth and fetal growth restriction. Although infection is a known cause of inflammation, a significant proportion of pregnancies have evidence of inflammation without any detectable infection. Inflammation can also be triggered by endogenous mediators, called damage associated molecular patterns or alarmins. One of these damage-associated molecular patterns, uric acid, is increased in the maternal circulation in pathological pregnancies and is a known agonist of the Nlrp3 inflammasome and inducer of inflammation. However, its effects within the placenta and on pregnancy outcomes remain largely unknown. We found that uric acid (monosodium urate [MSU]) crystals induce a proinflammatory profile in isolated human term cytotrophoblast cells, with a predominant secretion of IL-1\u03b2 and IL-6, a result confirmed in human term placental explants. The proinflammatory effects of MSU crystals were shown to be IL-1\u2013dependent using a caspase-1 inhibitor (inhibits IL-1 maturation) and IL-1Ra (inhibits IL-1 signaling). The proinflammatory effect of MSU crystals was accompanied by trophoblast apoptosis and decreased syncytialization. Correspondingly, administration of MSU crystals to rats during late gestation induced placental inflammation and was associated with fetal growth restriction. These results make a strong case for an active proinflammatory role of MSU crystals at the maternal\u2013fetal interface in pathological pregnancies, and highlight a key mediating role of IL-1. Furthermore, our study describes a novel in vivo animal model of noninfectious inflammation during pregnancy, which is triggered by MSU crystals and leads to reduced fetal growth.<\/jats:p>","DOI":"10.4049\/jimmunol.1601179","type":"journal-article","created":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T03:00:20Z","timestamp":1480561220000},"page":"443-451","source":"Crossref","is-referenced-by-count":82,"title":["Uric Acid Crystals Induce Placental Inflammation and Alter Trophoblast Function via an IL-1\u2013Dependent Pathway: Implications for Fetal Growth Restriction"],"prefix":"10.1093","volume":"198","author":[{"given":"Marie-Eve","family":"Brien","sequence":"first","affiliation":[{"name":"Ste-Justine Hospital Research Centre, Feto-Maternal and Neonatal Pathologies Research Axis, University of Montreal , Montreal, Quebec H3T 1C5,","place":["Canada"]},{"name":"Department of Obstetrics and Gynecology, University of Montreal , Montreal, Quebec H3T 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Montreal, Quebec H3T 1C5,","place":["Canada"]},{"name":"Department of Obstetrics and Gynecology, University of Montreal , Montreal, Quebec H3T 1C5,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Boufaied","sequence":"additional","affiliation":[{"name":"Ste-Justine Hospital Research Centre, Feto-Maternal and Neonatal Pathologies Research Axis, University of Montreal , Montreal, Quebec H3T 1C5,","place":["Canada"]},{"name":"Department of Obstetrics and Gynecology, University of Montreal , Montreal, Quebec H3T 1C5,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9e-Anne","family":"Hudon-Thibeault","sequence":"additional","affiliation":[{"name":"Institut de la Recherche Scientifique, Centre Institut Armand-Frappier , Laval, Quebec H7V 1B7,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Nadeau-Vall\u00e9e","sequence":"additional","affiliation":[{"name":"Ste-Justine Hospital Research Centre, Feto-Maternal and Neonatal Pathologies Research Axis, University of Montreal , Montreal, Quebec H3T 1C5,","place":["Canada"]},{"name":"Department of Pharmacology, University de Montreal , Montreal H3T 1C5,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy","family":"Vaillancourt","sequence":"additional","affiliation":[{"name":"Institut de la Recherche Scientifique, Centre Institut Armand-Frappier , Laval, Quebec H7V 1B7,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2713-0492","authenticated-orcid":false,"given":"Colin P","family":"Sibley","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre, University of Manchester , Manchester, M13 9WL,","place":["United Kingdom"]},{"name":"St. Mary\u2019s Hospital, Central Manchester University Hospital National Health Service Foundation Trust, Manchester Academic Health Science Centre , Manchester, M13 9WL,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikki M","family":"Abrahams","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine , CT 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8871-0589","authenticated-orcid":false,"given":"Rebecca L","family":"Jones","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre, University of Manchester , Manchester, M13 9WL,","place":["United Kingdom"]},{"name":"St. Mary\u2019s Hospital, Central Manchester University Hospital National Health Service Foundation Trust, Manchester Academic Health Science Centre , Manchester, 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