ArticleAmerican journal of reproductive immunology (New York, N.Y. : 1989)2019
Toll-like receptor 9, maternal cell-free DNA and myometrial cell response to CpG oligodeoxynucleotide stimulation.
Article in American journal of reproductive immunology (New York, N.Y. : 1989), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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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
8 citing papers in PubMed, 10 citations in OpenAlex.
- Determination of frequency of spontaneous resistance for gepotidacin and levofloxacin against a collection of gram-positive and gram-negative organisms.Antimicrobial agents and chemotherapy · 2026Article
- Decoding the immunological triad of TLRs, B1 cells, and feto-maternal microchimerism in pre-eclampsia pathogenesis: a narrative review.Frontiers in immunology · 2026Review
- sTLR9 on maternal Circulating immune cells as a negative regulatory phenotype during pregnancy.Cellular and molecular life sciences : CMLS · 2025Article
- Multidimensional roles of cfDNA fragmentomics in preeclampsia: from placental hypoxia and TLR9 inflammation to clinical risk stratification.Frontiers in medicine · 2025Review
- Stretch Causes cffDNA and HMGB1-Mediated Inflammation and Cellular Stress in Human Fetal Membranes.International journal of molecular sciences · 2024Article
- Polysaccharide-based nanomedicines for cancer immunotherapy: A review.Bioactive materials · 2021Review
- The Role of Danger Associated Molecular Patterns in Human Fetal Membrane Weakening.Frontiers in physiology · 2020Review
- The immunology of the fetal-placental unit comes of age.Clinical and experimental immunology · 2019Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
problemAmong mechanisms triggering onset of parturition, it has been recently postulated that Toll-Like Receptor (TLR)9 engagement by cell-free DNA (cfDNA) triggers inflammation, myometrial contractions, and labor in absence of infection. The current study evaluated whether direct (myometrial) or indirect (decidual) TLR9 engagement enhances human myometrial contractility. METHOD OF STUDY: Toll-like receptor 9 expression and cellular localization were surveyed by immunohistochemistry of placenta, fetal membranes, and myometrium in term (gestational age [GA]: >37 weeks) labor (TL, n = 7) or term non-labor (TNL, n = 7) tissues. Non-pregnant myometrium (n = 4) served as reference. TLR9 mRNA expression relative to other TLRs was evaluated through the mining of an RNA-seq dataset and confirmed by RT-PCR. Immortalized human myometrial cells (hTERT-HM) were treated with incremental concentrations of TLR9 agonist ODN2395, TNF-α, or LPS. Secreted cytokines were quantified by multiplex immunoassay, and contractility was assessed by an in-gel cell contraction assay (n = 9). Induction of hTERT-HM contractility was also evaluated indirectly following exposure to conditioned media from primary term decidual cells (n = 4) previously stimulated with ODN2395.
resultsToll-like receptor 9 immunostaining in placenta and amniochorion was strongest in decidual cells, but unrelated to labor. TLR9 staining intensity was significantly decreased in TL compared with TNL myometrium (P = 0.002). Although total cfDNA in maternal circulation increased in TL (P = 0.025 vs TNL), difference in cffDNA was non-significant. Myometrial TLR9 mRNA levels were unaffected by contractile status and far less abundant than other pro-inflammatory TLRs. hTERT-HM contractility was enhanced by LPS (P = 0.002) and TNF-α (P = 0.003), but not by ODN2395 (P = 0.345) or supernatant of TLR9-stimulated decidual cells.
conclusionMyometrial and decidual TLR9 are unlikely to directly regulate human parturition.
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Registered trials
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