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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Effects of prenatal lipopolysaccharide exposure on epithelial development and function in newborn rat intestine
Peter J Giannone1, Brandon L Schanbacher, John A Bauer
1Section of Neonatology, Department of Pediatrics, Center for Cardiovascular Medicine, Columbus Children's Research Institute, Columbus, Ohio 43205, USA. giannonep@pediatrics.ohio-state.edu
Insights
Prenatal exposure to lipopolysaccharide (LPS) in maternal rats significantly reduced intestinal thickness and increased gut permeability in newborn pups. This maternal infection model impacts neonatal intestinal development and function.
Area of Science:
- Neonatal physiology
- Maternal-fetal medicine
- Gastrointestinal development
Background:
- Maternal infections during pregnancy are linked to adverse neonatal outcomes, including lung and brain injury.
- Understanding the impact of prenatal infections on neonatal gut development is crucial for improving infant health.
Purpose of the Study:
- To investigate how maternal exposure to lipopolysaccharide (LPS) during pregnancy affects the intestinal development and function of newborn rats.
- To test the hypothesis that prenatal LPS exposure alters intestinal epithelial development and function.
Main Methods:
- Pregnant rats were injected with LPS or saline at E16.
- Newborn rat pups were assessed for morphometric parameters, inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine expression, and in vivo mucosal permeability.
- Measurements were taken at days of life 0, 3, 7, and 14.
Main Results:
- Prenatal LPS exposure led to significantly reduced distal ileal mucosal thickness in pups at days 0, 3, and 7.
- Increased iNOS and 3-nitrotyrosine protein concentrations were observed in the intestines of LPS-exposed pups.
- In vivo mucosal permeability, measured by serum fluorescein isothiocyanate (FITC) levels, was significantly higher in LPS-exposed pups at day 14.
Conclusions:
- Maternal LPS exposure during pregnancy significantly alters intestinal growth and development in newborn rats.
- The regulation of iNOS in the neonatal intestine is affected by prenatal exposure to LPS.
- Prenatal infection models provide insights into neonatal gut vulnerability and potential therapeutic targets.
Background:
Maternal infection during pregnancy is associated with several neonatal morbidities, including periventricular leukomalacia and lung maldevelopment and injury.
Objective:
To test the hypothesis that responses to prenatal maternal exposure to lipopolysaccharide (LPS) alter intestinal epithelial development and function in newborn rats.
Design/Methods:
Timed-pregnancy female Sprague-Dawley rats were administered either 2 mg LPS or an equal volume of isotonic saline by intraperitoneal injection at E16 and allowed to deliver naturally. Pups were weighed and then killed at days of life (DOL) 0, 3, 7 and 14. Morphometric parameters were measured on standard hematoxylin and eosin-stained sections using ImagePro software. Immunohistochemistry was performed with antibody specific for inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine on distal ileal intestinal samples analyzed at each time point. Optical density was determined and quantified for site-specific regions of intestinal sections. On DOL 14, in vivo mucosal permeability was measured by feeding rats fluorescein isothiocyanate (FITC) via orogastric tube; and then serum FITC was measured.
Results:
There were no significant differences in pup weights. Mucosal thicknesses were significantly less in the distal ileum from pups born to LPS-exposed dams on DOL 0, 3 and 7 (P < 0.001). On DOL 0, iNOS protein concentrations in the prenatal LPS treatment group were significantly greater than iNOS protein concentrations in the distal villus (P < 0.001), proximal villus/crypts (P < 0.01), submucosa (P < 0.001) and muscularis (P < 0.01) in the distal small intestine of the control group. On DOL 3, 7 and 14, significant differences were observed in iNOS protein concentrations in the distal villus and submucosal regions between groups (P < 0.001). On DOL 0, 3, 7 and 14, 3-nitrotyrosine immunostaining was significantly elevated in the prenatal LPS-exposed pups in the distal villus on (P < 0.001) as well as in the submucosa on DOL 3 (P < 0.001). Serum FITC measurement was significantly greater in prenatal LPS exposure group at DOL 14 (P < 0.001).
Conclusions:
Maternal exposure to LPS during pregnancy alters intestinal growth and regulation of iNOS in the newborn rat intestine.
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