265 EARLY LUNG DEVELOPMENT IN THE RAT AND ITS PERTURBATION BY NITROFEN EXPOSURE

Abstract

In search for mechanisms underlying pulmonary hypoplasia we have studied early lung development in the rat and its perturbation by Nitrofen exposure using serially sectioned embryos. The lung primordium is visible from day 12 of gestation, firstly as an outgrowth of the bottom of the larynx, and on day 13 as a triplicate tube growing in caudal direction. The longitudinal growth speed of the lungs exceed the growth of the whole embryo, resulting on day 15 in a longitudinal lung length of 20% of the embryo. During this period the lung primordium, is built up of undifferentiated epithelium surrounded by mesenchymal tissue. Exposure to Nitrofen on day 10 reduces the early proliferation and growth of the lung primordium, as measured in serial longitudinal sections of treated embryos. In fetuses that did not develop diaphragmatic hernia (DH) lung lenth had recovered to control range by day 20, irrespective of the Nitrofen dosage applied. In fetuses with leftsided DH, leftsided lung hypoplasia occurred in conjunction with right lungs that were significantly longer than controls. The results suggest two determinants of development of lung hypoplasia in this model; an early effect on proliferation of the lung primordum, and a late effect related to the presence of DH.