ArticleThe American journal of pathology2011
Complement activation triggers metalloproteinases release inducing cervical remodeling and preterm birth in mice.
Article in The American journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
118 citing papers in PubMed, 2 syntheses or guidelines pooled it, 184 citations in OpenAlex.
- Interventions for Infection and Inflammation-Induced Preterm Birth: a Preclinical Systematic Review.Reproductive sciences (Thousand Oaks, Calif.) · 2023Pooled it
- Vaginal progesterone vs. cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix, previous preterm birth, and singleton gestation: a systematic review and indirect comparison metaanalysis.American journal of obstetrics and gynecology · 2013Pooled it
- Evidence for participation of neutrophil gelatinase-associated lipocalin/matrix metalloproteinase-9 (NGAL•MMP-9) complex in the inflammatory response to infection in pregnancies complicated by preterm birth.American journal of reproductive immunology (New York, N.Y. : 1989) · 2016Trial
- Strain at the internal cervical os assessed with quasi-static elastography is associated with the risk of spontaneous preterm delivery at ≤34 weeks of gestation.Journal of perinatal medicine · 2015Trial
- Spleen-associated macrophage alterations and embryo viability in a murine model of recurrent spontaneous abortion.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Microbiota-dependent interferon-λ controls immunity of the uterus and maternal-fetal interface.Research square · 2026Article
- Complement and neutrophils are actively involved at the cervicovaginal interface in cases of adverse microbial composition, cervical shortening and spontaneous preterm birth.NPJ biofilms and microbiomes · 2026Article
- Comparative machine learning models for early prediction of preterm birth from maternal serum biomarkers.BMC pregnancy and childbirth · 2026Article
- Microbiota-dependent IFN-L controls uterine and placental immunity.bioRxiv : the preprint server for biology · 2026Article
- Arachidonic Acid-Induced Contraction of Smooth Muscle Is Mediated by MLC Phosphorylation in Preterm Birth.Journal of pregnancy · 2026Article
- Large number of CD68Medical molecular morphology · 2025Article
- Vaginal microbiome and preterm birth: Composition, mechanisms and microbiota‑directed therapies (Review).International journal of molecular medicine · 2025Review
- Complement C3 in panvascular disease: a central integrator of immune signaling and vascular remodeling.Clinical science (London, England : 1979) · 2025Review
- Complement Modulation Mitigates Inflammation-Mediated Preterm Birth and Fetal Neural Inflammation.Cells · 2025Article
- Collagen turnover during cervical remodeling involves both intracellular and extracellular collagen degradation pathways†.Biology of reproduction · 2025Article
- Article
- A bioprinted model of pregnant human uterine myometrium.Frontiers in bioengineering and biotechnology · 2025Article
- Review
- The presence of circulating human apolipoprotein J reduces the occurrence of cerebral microbleeds in a transgenic mouse model with cerebral amyloid angiopathy.Alzheimer's research & therapy · 2024Article
- The end is where we start from: withdrawal of 17-alpha hydroxyprogesterone caproate to prevent recurrent preterm birth.American journal of obstetrics and gynecology · 2024Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 5 countries.
Funding
Abstract
Inflammation is frequently linked to preterm delivery (PTD). Here, we tested the hypothesis that complement activation plays a role in cervical remodeling and PTD. We studied two mouse models of inflammation-induced PTD. The first model was induced by vaginal administration of lipopolysaccharide (LPS) and the second one by administration of progesterone antagonist RU486. Increased cervical C3 deposition and macrophages infiltration and increased serum C3adesArg and C5adesArg levels were observed in both models when compared to gestational age matched controls. A significant increase in collagen degradation, matrix metalloproteinase 9 (MMP-9) activity and tissue distensibility was observed in the cervix in both models. Mice deficient in complement receptor C5a did not show increased MMP-9 activity and cervical remodeling and did not deliver preterm in response to LPS or RU486, suggesting a role for C5aR in the cervical changes that precede PTD. In vitro studies show that macrophages release MMP-9 in response to C5a. Progesterone diminished the amount of C5aR on the macrophages surface, inhibited the release of MMP-9 and prevented PTD. In addition, macrophages depletion also prevented cervical remodeling and PTD in LPS-treated mice. Our studies show that C5a-C5aR interaction is required for MMP-9 release from macrophages, and the cervical remodeling that leads to PTD. Complement inhibition and supplementation with progesterone may be good therapeutic options to prevent this serious pregnancy complication.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.