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A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Endotoxin alters early fetal lung morphogenesis.
Christopher S Muratore1, Francois I Luks, Yonghong Zhou
1Department of Surgery, Pediatric Surgery, Hasbro Children's Hospital, Brown University, Providence, Rhode Island 02095, USA. christopher_muratore@brown.edu
The Journal of Surgical Research
|June 16, 2009
Summary
Early gestational exposure to lipopolysaccharides (LPS) impairs fetal rat lung development, affecting branching and potentially leading to bronchopulmonary dysplasia. This inflammation impacts endothelial cells and alters gene expression crucial for lung formation.
Area of Science:
- Developmental Biology
- Pulmonology
- Toxicology
Background:
- Premature lung hypoplasia and immaturity are exacerbated by inflammatory stimuli.
- Bronchopulmonary dysplasia can result from acute lung injury and metabolic issues.
- Previous studies focused on late gestational inflammation; this study examines early gestational effects.
Purpose of the Study:
- To investigate the impact of early gestational endotoxin exposure on fetal rat lung branching morphogenesis.
- To determine if lipopolysaccharides (LPS) affect lung development during the pseudoglandular stage.
Main Methods:
- Fetal rat lung explants from gestational day 15 were exposed to varying doses of LPS.
- Explants were examined daily using phase microscopy and fixed for histological analysis.
- Immunohistochemistry and real-time PCR assessed endothelial cells, growth factors, and inflammatory markers.
Main Results:
- LPS exposure caused dose-dependent airway sac contraction and interstitial thickening.
- High-dose LPS led to stunted branching, thickened airways, and increased matrix deposition.
- LPS increased COX-2 and iNOS expression while decreasing FGF9, FGF10, and FGFr2 gene expression.
Conclusions:
- Early fetal LPS exposure negatively impacts lung branching morphogenesis during the pseudoglandular phase.
- Inflammation affects fetal endothelial cells and suggests an inflammatory cascade involving COX-2.
- FGF-directed mechanisms may underlie abnormal lung development due to early inflammatory stimuli.
