ArticleAmerican journal of reproductive immunology (New York, N.Y. : 1989)2011
Placental viral infection sensitizes to endotoxin-induced pre-term labor: a double hit hypothesis.
Article in American journal of reproductive immunology (New York, N.Y. : 1989), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
91 citing papers in PubMed, 2 syntheses or guidelines pooled it, 135 citations in OpenAlex.
- Viruses in the female lower reproductive tract: a systematic descriptive review of metagenomic investigations.NPJ biofilms and microbiomes · 2024Pooled it
- A systematic review of immune-based interventions for perinatal neuroprotection: closing the gap between animal studies and human trials.Journal of neuroinflammation · 2023Pooled it
- Association of the eukaryotic vaginal virome with prophylactic antibiotic exposure and reproductive outcomes in a subfertile population undergoing in vitro fertilisation: a prospective exploratory study.BJOG : an international journal of obstetrics and gynaecology · 2020Trial
- Trial
- Effector and Activated T Cells Induce Preterm Labor and Birth That Is Prevented by Treatment with Progesterone.Journal of immunology (Baltimore, Md. : 1950) · 2019Trial
- Torque Teno Virus in the vagina: potential influence on health and disease.Clinics (Sao Paulo, Brazil) · 2026Review
- Trophoblast stem cells and syncytiotrophoblasts lack inflammatory responses to LPS but retain robust interferon-mediated antiviral immunity.Reproduction & fertility · 2026Article
- High-Throughput 3D-Printed Model of the Feto-Maternal Interface for the Discovery and Development of Preterm Birth Therapies.ACS applied materials & interfaces · 2024Article
- Palmitate and group BFrontiers in immunology · 2024Article
- SARS CoV-2 infection as a risk factor of preeclampsia and pre-term birth. An interplay between viral infection, pregnancy-specific immune shift and endothelial dysfunction may lead to negative pregnancy outcomes.Annals of medicine · 2023Review
- Intrinsic sexual dimorphism in the placenta determines the differential response to benzene exposure.iScience · 2023Article
- Diminished antiviral innate immune gene expression in the placenta following a maternal SARS-CoV-2 infection.American journal of obstetrics and gynecology · 2023Article
- The Medium Is the Message: Defining a "Normal" Vaginal Microbiome in Healthy Reproductive-Age Women.Reproductive sciences (Thousand Oaks, Calif.) · 2023Article
- Interferon epsilon and preterm birth subtypes; a new piece of the type I interferon puzzle during pregnancy?American journal of reproductive immunology (New York, N.Y. : 1989) · 2022Article
- Review
- Understanding the Immune System in Fetal Protection and Maternal Infections during Pregnancy.Journal of immunology research · 2022Review
- Stress-Related Herpesvirus Reactivation in Badgers Can Result in Clostridium Proliferation.EcoHealth · 2021Article
- Article
- ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in Infection-Associated Preterm Birth.Cells · 2021Article
- Cervical cytomegalovirus reactivation, cytokines and spontaneous preterm birth in Kenyan women.Clinical and experimental immunology · 2021Article
31 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
10 authors at 3 institutions in 2 countries.
Funding
Abstract
problemAmong pregnant women, acquired viral infections with a concurrent bacterial infection is a detrimental factor associated to poor prognosis. We evaluate the effect of a viral infection that does not lead to pre-term labor on the response to low doses of lipopolysaccharide (LPS). Our objectives were (i) to characterize the effect of a viral infection concurrent with exposure to microbial products on pregnancy outcome and (ii) to characterize the placental and fetal immune responses to the viral sensitization to LPS.
methodC57B/6 wild-type mice were injected with murine gammaherpesvirus 68 (MHV68) at E8.5. Either PBS or LPS was injected i.p. at E15.5. Pregnancy outcome and cytokine/chemokine profile from implantation sites were analyzed by multiplex.
resultsLPS treatment of MHV-68-infected animals induced pre-term delivery and fetal death in 100% of the mice. Pre-term labor was characterized by a upregulation of pro-inflammatory cytokines and chemokines in both placenta and decidua. Similar profiles were observed from MHV-68-infected human primary trophoblast and trophoblast cell lines in response to LPS.
conclusionWe describe for the first time that a sub-clinical viral infection in pregnant mice might sensitize to a bacterial infection leading to pre-term delivery. We propose the 'Double Hit Hypothesis' where the presence of a viral infection enhances the effect of bacterial products during pregnancy leading not only to pre-term labor but likely larger adverse outcomes.
Indexed as
Identifiers
What OpenQuestion holds
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.