ArticleEndocrinology2015
Toll-Like Receptor 4 Is an Essential Upstream Regulator of On-Time Parturition and Perinatal Viability in Mice.
Article in Endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 69 citations in OpenAlex.
- The Maternal Microbiome in Pregnancy: From Physiological Changes to Dysbiosis and Obstetrical Complications-Therapeutic Perspectives.Life (Basel, Switzerland) · 2026Review
- Physiological functions of seminal vesicle secretions in male fertility.Histology and histopathology · 2026Review
- Polymorphism in the TLR Adaptors of the Toll Signalling Pathway for Use in Livestock Breeding for Health Traits.International journal of molecular sciences · 2026Review
- Vaginal microbiome and preterm birth: Composition, mechanisms and microbiota‑directed therapies (Review).International journal of molecular medicine · 2025Review
- Exploratory Evaluation of Circulating Microbiota-Derived Corisin Levels in Women with Adverse Pregnancy Outcomes.Antioxidants (Basel, Switzerland) · 2025Article
- Article
- Association of Variants in Innate Immune GenesGenes · 2023Article
- Simultaneous CRISPR screening and spatial transcriptomics reveals intracellular, intercellular, and functional transcriptional circuits.bioRxiv : the preprint server for biology · 2023Article
- Emerging role of toll-like receptors signaling and its regulators in preterm birth: a narrative review.Archives of gynecology and obstetrics · 2023Review
- Chlamydia trachomatis antigen induces TLR4-TAB1-mediated inflammation, but not cell death, in maternal decidua cells.American journal of reproductive immunology (New York, N.Y. : 1989) · 2023Article
- Review
- The maternal-placental-fetal interface: Adaptations of the HPA axis and immune mediators following maternal stress and prenatal alcohol exposure.Experimental neurology · 2022Review
- The immunobiology of preterm labor and birth: intra-amniotic inflammation or breakdown of maternal-fetal homeostasis.Reproduction (Cambridge, England) · 2022Review
- A Review of Delayed Delivery Models and the Analysis Method in Mice.Journal of developmental biology · 2022Review
- Article
- Article
- Macrophages exert homeostatic actions in pregnancy to protect against preterm birth and fetal inflammatory injury.JCI insight · 2021Article
- Toll-like receptor-4 null mutation causes fetal loss and fetal growth restriction associated with impaired maternal immune tolerance in mice.Scientific reports · 2021Article
- Article
- TLR4-Endothelin Axis Controls Syncytiotrophoblast Motility and Confers Fetal Protection in Placental Malaria.Infection and immunity · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
An inflammatory response is instrumental in the physiological process of parturition but the upstream signals initiating inflammation are undefined. Because endogenous ligands for Toll-like receptor 4 (TLR4) are released in late gestation, we hypothesized that on-time labor requires TLR4 signaling, to trigger a cytokine and leukocyte response and accelerate the parturition cascade. In pregnant TLR4-deficient (Tlr4-/-) mice, average gestation length was extended by 13 hours and increased perinatal mortality was seen compared with wild-type controls. Quantification of cytokine and uterine activation gene expression showed that late gestation induction of Il1b, Il6, Il12b, and Tnf expression seen in control placenta and fetal membranes was disrupted in Tlr4-/- mice, and accompanied by a transient delay in expression of uterine activation genes, including prostaglandin F receptor, oxytocin receptor, and connexin-43. Leukocyte populations were altered before birth in TLR4-deficient females, with fewer neutrophils and macrophages in the placenta, and fewer dendritic cells and more regulatory T cells in the myometrium. Administration of TLR4 ligand lipopolysaccharide to pregnant wild-type mice induced cytokine expression and fetal loss, whereas Tlr4-/- pregnancies were protected. The small molecule TLR4 antagonist (+)-naloxone increased mean duration of gestation by 16 hours in wild-type mice. Collectively, these data demonstrate that TLR4 is a key upstream regulator of the inflammatory response acting to drive uterine activation and control the timing of labor. Because causal pathways for term and preterm labor converge with TLR4, interventions to manipulate TLR4 signaling may have therapeutic utility for women at risk of preterm labor, or in postterm pregnancy.
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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.