ArticleThe Journal of clinical investigation2013
Combinatory approaches prevent preterm birth profoundly exacerbated by gene-environment interactions.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Different exposure levels of fine particulate matter and preterm birth: a meta-analysis based on cohort studies.Environmental science and pollution research international · 2017Pooled it
- Identification of cell senescence-related genes in spontaneous preterm birth based on bioinformatics analysis and machine learning.PloS one · 2026Article
- Regulatory Interplay of p53, AMPK, and mTOR in Decidualization: Implications for Reproductive Competence and Cancer Biology.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- Elevated NGF provokes decidual lipid peroxidation and promotes preterm birth in mice.Journal of translational medicine · 2025Article
- Stage-specific autophagy dynamics in reproductive processes and associated disorders.Frontiers in cell and developmental biology · 2025Review
- mTOR inhibitors as potential therapeutics for endometriosis: a narrative review.Molecular human reproduction · 2024Review
- Deciphering decidual deficiencies in recurrent spontaneous abortion and the therapeutic potential of mesenchymal stem cells at single-cell resolution.Stem cell research & therapy · 2024Article
- Review
- Is human labor at term an inflammatory condition?†.Biology of reproduction · 2023Review
- The Regulators of Human Endometrial Stromal Cell Decidualization.Biomolecules · 2022Review
- PGRMC1 Regulates Cellular Senescence via Modulating FOXO1 Expression in Decidualizing Endometrial Stromal Cells.Biomolecules · 2022Article
- Spontaneous preterm birth: Involvement of multiple feto-maternal tissues and organ systems, differing mechanisms, and pathways.Frontiers in endocrinology · 2022Review
- Single-cell transcriptome analysis reveals defective decidua stromal niche attributes to recurrent spontaneous abortion.Cell proliferation · 2021Article
- Uterine Notch2 facilitates pregnancy recognition and corpus luteum maintenance via upregulating decidual Prl8a2.PLoS genetics · 2021Article
- Maternal regulation of inflammatory cues is required for induction of preterm birth.JCI insight · 2020Article
- Pathogenesis of preterm birth: bidirectional inflammation in mother and fetus.Seminars in immunopathology · 2020Review
- Physiological and pathological regulation of autophagy in pregnancy.Archives of gynecology and obstetrics · 2020Review
- The link between endometrial stromal cell senescence and decidualization in female fertility: the art of balance.Cellular and molecular life sciences : CMLS · 2020Review
- Automated mass spectrometry imaging of over 2000 proteins from tissue sections at 100-μm spatial resolution.Nature communications · 2020Article
- Antibiotic administration can eradicate intra-amniotic infection or intra-amniotic inflammation in a subset of patients with preterm labor and intact membranes.American journal of obstetrics and gynecology · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
There are currently more than 15 million preterm births each year. We propose that gene-environment interaction is a major contributor to preterm birth. To address this experimentally, we generated a mouse model with uterine deletion of Trp53, which exhibits approximately 50% incidence of spontaneous preterm birth due to premature decidual senescence with increased mTORC1 activity and COX2 signaling. Here we provide evidence that this predisposition provoked preterm birth in 100% of females exposed to a mild inflammatory insult with LPS, revealing the high significance of gene-environment interactions in preterm birth. More intriguingly, preterm birth was rescued in LPS-treated Trp53-deficient mice when they were treated with a combination of rapamycin (mTORC1 inhibitor) and progesterone (P4), without adverse effects on maternal or fetal health. These results provide evidence for the cooperative contributions of two sites of action (decidua and ovary) toward preterm birth. Moreover, a similar signature of decidual senescence with increased mTORC1 and COX2 signaling was observed in women undergoing preterm birth. Collectively, our findings show that superimposition of inflammation on genetic predisposition results in high incidence of preterm birth and suggest that combined treatment with low doses of rapamycin and P4 may help reduce the incidence of preterm birth in high-risk women.
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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.