ULTRASTRUCTURAL FEATURES OF ALVEOLAR EPITHELIAL-CELLS IN THE LATE FETAL PULMONARY ACINUS - A COMPARISON BETWEEN NORMAL AND HYPOPLASTIC LUNGS USING A RAT MODEL OF PULMONARY HYPOPLASIA AND CONGENITAL DIAPHRAGMATIC-HERNIA

The aim of this study was to describe and compare the ultrastructural features and functional maturity of alveolar epithelial cells in hypop lastic and normal fetal rat lungs. Pulmonary hypoplasia in association with congenital diaphragmatic hernia was induced in fetuses by admini stration of 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen) to pregna nt Sprague Dawley rats (100 mg on day 10 of gestation). Lung tissue of Nitrofen-exposed and control fetal rats aged 19-22 days (vaginal plug day 1, birth day 23) was embedded in Epon. Semithin (1 mum) toluidine blue-stained sections were examined by light microscopy; ultrathin se ctions (approximately 80 nm) were studied via transmission electron mi croscopy. In bronchoalveolar lavage fluid from control and Nitrofen-ex posed fetuses (day 22), phospholipid fractions and surfactant protein A content were measured semiquantitatively. On day 19 both control and Nitrofen-exposed lungs contained only cuboid alveolar epithelial cell s; from day 20 there were cuboid, low cuboid, and thinner epithelial c ells. The (low) cuboid cells contained large glycogen fields, some pre cursory stages of multilamellar bodies (MLBs), and just a few mature M LBs on day 19 and 20; smaller glycogen fields, more precursory stages, and more mature MLBs on day 21; and little or no glycogen but many pr ecursory stages and mature MLBs on day 22. The thinner cells contained little or no glycogen and a few precursory stages of MLBs on days 20- 22; very thin cells on day 22 contained neither glycogen nor any precu rsory stages of MLBs. MLBs and tubular myelin were seen in the lumens of future air spaces from day 20 onward. Nitrofen-exposed lungs differ ed from control lungs in that inclusion bodies (IBs) were less numerou s in (low) cuboid alveolar cells on days 19 and 20, and more glycogen was seen on day 22. In addition intra- and extracellular ''MLBs'' in e xposed lungs more often had an unusual appearance, i.e., a confluent s tructure and higher electron density. However, despite morphologic dif ferences, there was no clear difference in phospholipid composition an d SP-A content per mol phospholipid in bronchoalveolar lavage fluid. W e conclude that morphologically hypoplastic lungs are less mature near term, without an apparent effect on surfactant composition. (C) 1993 Wiley-Liss, Inc.