Lung hypoplasia in the nitrofen model of congenital diaphragmatic hernia occurs early in development
1 Department of Medicine, National Jewish Medical and Research Center, and 2 Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80206 The teratogen nitrofen produces a congenital diaphragmatic hernia (CDH) and pulmonary hypopl...
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Published in | American journal of physiology. Lung cellular and molecular physiology Vol. 279; no. 6; pp. 1159 - L1171 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
01.12.2000
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Subjects | |
Online Access | Get full text |
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Summary: | 1 Department of Medicine, National Jewish Medical and
Research Center, and 2 Division of Pulmonary Sciences and
Critical Care Medicine, University of Colorado Health Sciences
Center, Denver, Colorado 80206
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.
lung branching; pulmonary hypoplasia; surfactant proteins; vascular
endothelial growth factor; Flk-1; Flt-1; development |
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ISSN: | 1040-0605 1522-1504 |
DOI: | 10.1152/ajplung.2000.279.6.l1159 |