Impaired spreading of surfactant phospholipids in the lungs of newborn rats with pulmonary hypoplasia as a model of congenital diaphragmatic hernia induced by nitrofen

In order to clarify the pathological outcome of congenital diaphragmatic he rnia (CDH), we devised an animal model of CDH by administration of 2,4-dich lorophenyl-p-nitrophenyl ether (nitrofen) to pregnant rats, and determined the level and distribution of lung surfactant using the monoclonal antibody toward sphingomyelin and disaturated phosphatidylcholine (disat-PC), In co ntrol rats, the concentration of disat-PC was found to increase greatly fro m 16 to 18 days of gestation. Intragastric administration of nitrofen to pr egnant rats at day 9 of gestation resulted in CDH in 42.7% of fetuses deliv ered after 20 days of gestation. In nitrofen-treated fetuses, the concentra tion of disat-PC in the lungs was lower than those in control fetuses, and surfactant apoprotein SP-A was similarly reduced in nitrofen-treated fetuse s. However, the concentration of disat-PC in nitrofen-treated fetuses was h igher than that in control fetuses at 18 days of gestation, indicating a sy nthetic potential of surfactant in nitrofen-treated fetuses comparable to t hat at the late stage of normal gestation. Immunohistochemical study with t he antibody revealed that surfactant phospholipid was mainly in the form of intracellular granules in nitrofen-treated fetuses, probably causing the h ypoplastic lungs and then CDH, in contrast to the uniform distribution on t he pulmonary alveolar surface in control fetuses. (C) 2001 Elsevier Science B.V. All rights reserved.