Fetal tracheal occlusion in the rat model of nitrofen-induced congenital diaphragmatic hernia.
Prenatal tracheal occlusion (TO) consistently accelerates lung growth in the sheep model of congenital diaphragmatic hernia (CDH). However, significant variability in lung growth has been observed in early clinical trials of TO. We hypothesized that lung hypoplasia created at relatively late stages of lung development may not be equivalent to human CDH-induced lung hypoplasia, which begins early in gestation. To test this hypothesis, we performed TO in the rat model of nitrofen-induced CDH. Left-sided CDH was induced by administering 100 mg of nitrofen to timed pregnant rats on day 9 of gestation. On day 19 of gestation, four to five fetuses per dam underwent surgical ligation of the trachea. At death (day 21.5), lungs from non-CDH (non-CDH group), left-CDH (CDH group), and trachea-occluded left-CDH fetuses (CDH-TO group) were harvested and compared by weight, DNA and protein content, and stereological morphometry. Wet and dry lung weight-to-body weight ratio, total lung DNA and protein contents, the volume of lung parenchyma, and the total saccular surface area of the CDH-TO group were significantly increased relative to the CDH group and were either greater than or comparable to the non-CDH controls. We conclude that TO accelerates lung growth and increases lung parenchyma in an early-onset model of CDH-induced lung hypoplasia.
Kitano
Y
Y
The Children's Institute for Surgical Science and The Center for Fetal Diagnosis and Treatment, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-4399, USA.
Davies
P
P
von Allmen
D
D
Adzick
N S
NS
Flake
A W
AW
D000818:Animals; D001835:Body Weight; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D005315:Fetal Diseases / Q000601:surgery; D006548:Hernia, Diaphragmatic / Q000139:chemically induced; D065630:Hernias, Diaphragmatic, Congenital; D006651:Histocytochemistry; D008168:Lung / Q000196:embryology / Q000473:pathology; D009929:Organ Size; D010647:Phenyl Ethers; D011247:Pregnancy; D011506:Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000196:embryology / Q000473:pathology; D014135:Tracheal Stenosis / Q000151:congenital* / Q000601:surgery
D010647:Phenyl Ethers; D011506:Proteins; D004247:DNA; C007350:nitrofen