ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2014
Chorioamnionitis-induced fetal gut injury is mediated by direct gut exposure of inflammatory mediators or by lung inflammation.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 60 citations in OpenAlex.
- Fetal inflammatory response severity on placental histology identifies neonates at risk for meconium aspiration syndrome.Pediatric research · 2026Article
- Interleukin-1 Receptor Antagonists Partially Inhibited Histological Injury but Not Tissue Inflammation in a Sheep Model of Pregnancy.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Investigating pulmonary inflammation and injury after progressive systemic inflammation in preterm fetal sheep.Frontiers in physiology · 2025Article
- Homeostatic Macrophages Prevent Preterm Birth and Improve Neonatal Outcomes by Mitigating In Utero Sterile Inflammation in Mice.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Blockade of IL-6R prevents preterm birth and adverse neonatal outcomes.EBioMedicine · 2023Article
- Disrupted metabolic signatures in amniotic fluid associated with increased risk of intestinal inflammation in cesarean section offspring.Frontiers in immunology · 2023Article
- Effects of multiple pro-inflammatory stimuliFrontiers in immunology · 2023Article
- Perinatal Hyperoxia and Developmental Consequences on the Lung-Brain Axis.Oxidative medicine and cellular longevity · 2022Review
- Evidence of both foetal inflammation and hypoxia-ischaemia is associated with meconium aspiration syndrome.Scientific reports · 2021Article
- Amniotic fluid interleukin 6 and interleukin 8 are superior predictors of fetal lung injury compared with maternal or fetal plasma cytokines or placental histopathology in a nonhuman primate model.American journal of obstetrics and gynecology · 2021Article
- Understanding Host-Pathogen Interactions in Acute Chorioamnionitis Through the Use of Animal Models.Frontiers in cellular and infection microbiology · 2021Review
- Article
- Chorioamnionitis induces enteric nervous system injury: effects of timing and inflammation in the ovine fetus.Molecular medicine (Cambridge, Mass.) · 2020Article
- Pulmonary Consequences of Prenatal Inflammatory Exposures: Clinical Perspective and Review of Basic Immunological Mechanisms.Frontiers in immunology · 2020Review
- Chronic Intra-UterineFrontiers in immunology · 2020Article
- Postnatal Gut Immunity and Microbiota Development Is Minimally Affected by Prenatal Inflammation in Preterm Pigs.Frontiers in immunology · 2020Article
- Mechanisms of Fetal T Cell Tolerance and Immune Regulation.Frontiers in immunology · 2020Review
- Prenatal Endotoxin Exposure Induces Fetal and Neonatal Renal Inflammation via Innate and Th1 Immune Activation in Preterm Pigs.Frontiers in immunology · 2020Article
- Fetal exposure to maternal inflammation interrupts murine intestinal development and increases susceptibility to neonatal intestinal injury.Disease models & mechanisms · 2019Article
- CD161 contributes to prenatal immune suppression of IFNγ-producing PLZF+ T cells.The Journal of clinical investigation · 2019Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Intra-amniotic exposure to proinflammatory agonists causes chorioamnionitis and fetal gut inflammation. Fetal gut inflammation is associated with mucosal injury and impaired gut development. We tested whether this detrimental inflammatory response of the fetal gut results from a direct local (gut derived) or an indirect inflammatory response mediated by the chorioamnion/skin or lung, since these organs are also in direct contact with the amniotic fluid. The gastrointestinal tract was isolated from the respiratory tract and the amnion/skin epithelia by fetal surgery in time-mated ewes. Lipopolysaccharide (LPS) or saline (controls) was selectively infused in the gastrointestinal tract, trachea, or amniotic compartment at 2 or 6 days before preterm delivery at 124 days gestation (term 150 days). Gastrointestinal and intratracheal LPS exposure caused distinct inflammatory responses in the fetal gut. Inflammatory responses could be distinguished by the influx of leukocytes (MPO(+), CD3(+), and FoxP3(+) cells), tumor necrosis factor-α, and interferon-γ expression and differential upregulation of mRNA levels for Toll-like receptor 1, 2, 4, and 6. Fetal gut inflammation after direct intestinal LPS exposure resulted in severe loss of the tight junctional protein zonula occludens protein 1 (ZO-1) and increased mitosis of intestinal epithelial cells. Inflammation of the fetal gut after selective LPS instillation in the lungs caused only mild disruption of ZO-1, loss in epithelial cell integrity, and impaired epithelial differentiation. LPS exposure of the amnion/skin epithelia did not result in gut inflammation or morphological, structural, and functional changes. Our results indicate that the detrimental consequences of chorioamnionitis on fetal gut development are the combined result of local gut and lung-mediated inflammatory responses.
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