Document Detail


Lung hypoplasia in the nitrofen model of congenital diaphragmatic hernia occurs early in development.
MedLine Citation:
PMID:  11076806     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The teratogen nitrofen produces a congenital diaphragmatic hernia (CDH) and pulmonary hypoplasia in rodent fetuses that closely parallel observations made in humans. We hypothesized that these changes may be due to primary pulmonary hypoplasia and not herniation of the abdominal contents. Timed-pregnant rats were given nitrofen on day 9, and fetuses were harvested on days 13 through 21. Initial evagination of lung buds on gestational day 11 was not delayed in nitrofen-treated fetuses. On gestational day 13, however, there was a significant decrease in the number of terminal end buds in the lungs of nitrofen-exposed fetuses vs. controls. Thymidine-labeled lung epithelial and mesenchymal cells were significantly decreased in nitrofen-treated lungs. Lungs from nitrofen-treated fetuses exhibited wide septae with disorganized, compacted tissue, particularly around the air spaces. Expression of surfactant protein B and C mRNAs was significantly decreased in the nitrofen litters. In situ hybridization of fetal lung tissue at all gestational ages showed no difference in the expression of vascular endothelial growth factor, Flk-1, or Flt-1 mRNAs. Because closure of the diaphragm is completed on gestational day 16 in the rat, our results suggest that lung hypoplasia in this model of CDH is due at least in part to a primary effect of nitrofen on the developing lung.
Authors:
T W Guilbert; S A Gebb; J M Shannon
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  279     ISSN:  1040-0605     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2000-12-01     Completed Date:  2000-12-22     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  L1159-71     Citation Subset:  IM    
Affiliation:
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA. guilbert@resep-sci.arizona.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Division / drug effects
Disease Models, Animal
Endothelial Growth Factors / genetics
Extracellular Matrix Proteins / genetics
Female
Fetus / drug effects,  pathology,  ultrastructure
Gene Expression Regulation, Developmental / drug effects
Gestational Age
Hernia, Diaphragmatic / chemically induced,  congenital,  pathology*
Lung / embryology*,  pathology*,  ultrastructure
Lymphokines / genetics
Microscopy, Electron
Peptides / genetics
Pesticides*
Phenyl Ethers*
Pregnancy
Protein Precursors / genetics
Proteolipids / genetics
Pulmonary Surfactants / genetics
RNA, Messenger / analysis
Rats
Rats, Sprague-Dawley
Receptor Protein-Tyrosine Kinases / genetics
Receptors, Growth Factor / genetics
Receptors, Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factors
Grant Support
ID/Acronym/Agency:
HL-57144/HL/NHLBI NIH HHS; R01-HL45011/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Endothelial Growth Factors; 0/Extracellular Matrix Proteins; 0/Lymphokines; 0/Peptides; 0/Pesticides; 0/Phenyl Ethers; 0/Protein Precursors; 0/Proteolipids; 0/Pulmonary Surfactants; 0/RNA, Messenger; 0/Receptors, Growth Factor; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors; 0/surfactant protein B propeptide; 133135-52-1/Sftpc protein, rat; 1836-75-5/nitrofen; EC 2.7.10.1/Flt1 protein, rat; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases; EC 2.7.10.1/Receptors, Vascular Endothelial Growth Factor; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-1

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