Lung growth and maturation in the rat model of experimentally induced congenital diaphragmatic hernia.
This paper explores whether, in addition to the previously described lung hypoplasia with arteriolar hypermuscularization present in the nitrofen-induced foetal rat model of congenital diaphragmatic hernia (CDH), there are changes in the respiratory exchange epithelium, consistent with the hypothesis that abnormal surfactant production and/or release could account in part for the respiratory insufficiency in this condition. Foetal lungs from nitrofen-treated rats were obtained on the 21st day of gestation, weighed and processed for light and electron-microscopic studies and compared to controls of the same age. Tissues from 29 control and 26 CDH foetuses were examined. In addition, lungs from 19 foetuses born to nitrofen-treated dams but without CDH were also studied. The lungs from CDH animals were hypoplastic by weight in comparison with control ones and so were those from treated foetuses without CDH. Airway branching was arrested in CDH at the pseudo-glandular stage of development, corresponding to the 16th day of gestation and the very narrow air spaces were lined by generally mature type II pneumocytes rich in glycogen and lamellar bodies corresponding to the 19th day of gestation. This pattern was in contrast to that of the control foetuses which had a normal terminal sac pattern with flat type I pneumocyte lining corresponding to their gestational age. Nitrofentreated animals without CDH had intermediate patterns. These findings support the hypothesis that the surfactant-producing system has the same lesions in this experimental model as in other less-affordable ones, like the foetal lamb one. Further studies on the contribution of this factor to the altered respiratory physiology in CDH using this model are warranted.
Alfonso
L F
LF
Universidad del País Vasco, Hospital NaSa de Aranzazu, San Sebastián, Spain.
Vilanova
J
J
Aldazabal
P
P
Lopez de Torre
B
B
Tovar
J A
JA
D000818:Animals; D003964:Diaphragm / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005865:Gestational Age; D006540:Herbicides; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000473:pathology; D065630:Hernias, Diaphragmatic, Congenital; D008168:Lung / Q000002:abnormalities* / Q000187:drug effects / Q000473:pathology; D010647:Phenyl Ethers; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D006540:Herbicides; D010647:Phenyl Ethers; D011663:Pulmonary Surfactants; C007350:nitrofen