Changes in lung structure and cellular division induced by tracheal obstruction in fetal sheep

Increased expansion of the fetal lung, caused by obstruction of the fetal t rachea, is a potent stimulus for growth and structural development of the f etal lung. Our aim was to analyze the changes in lung structure induced by fetal tracheal obstruction and to identify cell types that contribute to th e growth response. Fetal sheep were exposed to 2, 4, or 10 days of tracheal obstruction (TO) and on day 128 of gestation (term "147 d"), mere injected with H-3-thymidine 8 hours before tissues were collected. The right lung w as fixed at 20 cm H2O and prepared for stereological and autoradiographic a nalysis. Alveolar wall thickness (7.8 +/- 0.3 mu m vs 5.5 +/- 0.4 mu m) and percent tissue space (27.9 +/- 0.9% vs 21.4 +/- 2.8%) were increased at 2 days of TO, but were not different from control at 4 and 10 days. The lumin al surface area of the right lung increased gradually from 2.4 +/- 0.2 m(2) /kg in control fetuses to 3.6 +/- 0.4 m(2)/kg following 10 days of 10 and t his increase was accompanied by an increase in alveolar number (control: 80 8 x 10(6) +/- 81.9 x 10(6) vs 10d obstruct: 1254 x 10(6) +/- 63 x 10(6)). A lveolar diameter increased at 2 days of 10 (51.8 +/- 1.4 mu m vs 43.8 +/- 1 .9 mu m), but was not increased further at 4 or 10 days. The percentage of dividing cells was increased at 2 days of TO (12.64 +/- 3.39% vs 1.73 +/- 0 .31%), remained elevated at 4 days (5.01 +/- 0.27%), but had returned to co ntrol by day 10. The increase at 2 days was due to division of type II epit helial cells, fibroblasts, and endothelial cells. We conclude that increase d expansion of the fetal lung induces time-dependent changes in lung struct ure and cell division rates; these include a transient increase in alveolar wall thickness, a rapid increase in alveolar number, and a gradual increas e in luminal surface area. The latter is probably caused by an increase in alveolar number rather than an increase in the alveolar size.