ArticleJournal of immunology (Baltimore, Md. : 1950)2017
Uric Acid Crystals Induce Placental Inflammation and Alter Trophoblast Function via an IL-1-Dependent Pathway: Implications for Fetal Growth Restriction.
Article in Journal of immunology (Baltimore, Md. : 1950), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Maternal hyperuricemia and adverse maternal-fetal outcomes: a systematic review and meta-analysis of observational studies.Frontiers in medicine · 2026Pooled it
- Effects of Common Therapies for Threatened Preterm Labor on the Placental Inflammatory Response.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Article
- NLRP3 inflammasome characterization in first-trimester, preterm, and term human villous placenta.Scientific reports · 2026Article
- Inflammation at the Maternal-Fetal Interface: Mechanisms Linking Maternal-Fetal Immunity to Preeclampsia and Fetal Growth Restriction.International journal of molecular sciences · 2026Review
- Pregnancy outcomes after maternal and paternal anti-IL-1 treatment exposure in cryopyrin-associated periodic syndromes (CAPS).Rheumatology (Oxford, England) · 2025Article
- Association between uric acid to high-density lipoprotein cholesterol ratio (UHR) and female infertility: insights from a cross-sectional study.European journal of medical research · 2025Article
- Placental Inflammation in Preterm Premature Rupture of Membranes and Risk of Neurodevelopmental Disorders.Cells · 2025Review
- Plasma Extracellular Vesicles from Preeclamptic Patients Trigger a Detrimental Crosstalk Between Glomerular Endothelial Cells and Podocytes Involving Endothelin-1.International journal of molecular sciences · 2025Article
- Understanding a Potential Role for the NLRP3 Inflammasome in Placenta-Mediated Pregnancy Complications.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025Review
- Assessıng the predıctıve accuracy of blood-based bıomarkers ın neonatal outcomes for pregestatıonal dıabetes mellıtus.Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia · 2025Article
- Trophoblast fusion in fetal growth restriction is inhibited by CTGF in a cell-cycle-dependent manner.Journal of molecular histology · 2024Article
- Predictive biomarkers and initial analysis of maternal immune alterations in postpartum preeclampsia reveal an immune-driven pathology.Frontiers in immunology · 2024Article
- Decidual macrophages and Hofbauer cells in fetal growth restriction.Frontiers in immunology · 2024Review
- Decoding connections in the European population: serum uric acid, sex hormone-binding globulin, total testosterone, estradiol, and female infertility - advanced bidirectional and mediative Mendelian randomization.Frontiers in endocrinology · 2024Article
- Gasdermin D promotes hyperuricemia-induced renal tubular injury through RIG-I/caspase-1 pathway.iScience · 2023Article
- Article
- Review
- The role of interleukin-1 in perinatal inflammation and its impact on transitional circulation.Frontiers in pediatrics · 2023Review
- Review
- Role of Uric Acid Levels in the Development of Gestational Diabetes Mellitus: A Review.Cureus · 2022Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
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-1β and IL-6, a result confirmed in human term placental explants. The proinflammatory effects of MSU crystals were shown to be IL-1-dependent 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-fetal 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.
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Registered trials
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