Congenital Diaphragmatic Hernia Induced by Nitrofen in Mice and Rats: Characteristics as Animal Model and Pathogenetic Relationship between Diaphragmatic Hernia and Lung Hypoplasia

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Abstract
Congenital diaphragmatic hernia (CDH) and lung hypoplasia were induced in high frequency and dose‐dependently in the offspring from dams, treated orally with 2,4‐dichlorophenyl‐p‐nitrophenyl ether (nitrofen) during pregnancy in CD‐I mice and CD rats. Both in mice and rats, CDH found in the fetal and neonatal periods was a posterolateral type of diaphragmatic hernia (DH) showing a distinct side‐preponderance: the left‐side preponderance in mice and right‐side preponderance in rats. CDH in the offspring, surviving after weaning, was mostly of retrosternal type in mice and of pericardial type in rats. CDH induced experimentally in the present study can be regarded as an excellent animal model for human CDH in terms of both anatomical features and the time of appearance of different types of CDH as well as clinical symptoms.Lung hypoplasia was observed in the offspring with and without CDH; though its severity was greater in those with CDH. The offspring with severe lung hypoplasia died of respiratory insufficiency during the neonatal period, regardless of the presence or absence of CDH. These findings suggest that lung hypoplasia is not a consequence of CDH, but that a common pathogenetic process in the early embryonic stage might involve both lung hypoplasia and CDH.