Congenital Diaphragmatic Hernia in Rats Using Nitrofen: An Animal Model

ABSTRACT

PURPOSE: Since 1971, Nitrofen (2,4-dichloro-4`-nitrodiphenyl ether) herbicide has been known to induce variable congenital abnormalities in rats. However, until now there has been no animal model of congenital diaphragmatic hernia (CDH) using this herbicide in Korea. Therefore, CDH in rats using Nitrofen was tried for searching on pathogenesis or using therapeutic modalities of CDH. METHODS: 20 Sprague-Dawley rats ingested Nitrofen as indicated on the 9.5th day of gestation, and after sacrificing on the 21th day of gestation. 243 offspring were harvested for the examination of diaphragmatic herniations. Dissections were made along sites of herniations to confirm the diaphragmatic herniation's site and size, lung/body weight ratio comparison as well as to accomplish microscopic radial saccular counting and evaluation of alveolar septal wall maturations and a comparision was made between the groups. RESULTS: CDH appeared in 149 of 243 offspring. CDH only appeared in the posterior portion of the diaphragm regardless of size or the side of appearance. Left sided CDH was the most common single diaphragmatic anomaly, represented in 112 offspring. Right sided CDH was next, found in 31 offspring, and bilateral CDH was seen in 6 offspring. Left sided CDH was almost always associated with visceral herniations and with pulmonary hypoplasia on the affected side, which was proved in the decreased Lung/Body weight ratio and in decreased radial saccular counts and in increased alveolar septal wall thickness in the affected lungs of CDH. In94 offspring without CDH following exposure to Nitrofen, moderate pulmonary hypo plasia was microscopically observed. CONCLUSION: Initial Rat modeling of congenital diaphragmatic hernia using Nitrofen showed results of herniation and pulmonary hypoplasia of the affected lungs acceptable for further experimental studies on CDH and accompaning pulmonary abnormalities.