Effect of increased lung expansion on lung growth and development near midgestation in fetal sheep

Obstruction of the fetal trachea is a potent stimulus for fetal lung growth and may have therapeutic potential in human fetuses with lung hypoplasia. However, the effects of increased lung expansion on lung development near m idgestation, which is the preferred timing for fetal intervention, have not been well studied. Our aim was to determine the effects of increased lung expansion on lung development at 75-90 d of gestation in fetal sheep. In th ree groups of fetuses (n = 4 for each), the trachea was occluded for either 10 [10-d tracheal occlusion (TO) group] or 15 d (15-d TO group) or left in tact (control fetuses). TO for both 10 and 15 d caused fetal hydrops, resul ting in significantly increased fetal body weights. Both periods of TO sign ificantly increased total lung DNA contents from 99.8 +/- 10.1 to 246.0 +/- 5.3 and 246.9 +/- 48.7 mg in 10- and 15-d TO fetuses, respectively. TO for 10 and 15 d also increased airspace diameter, although the percentage of l ung occupied by airspace was not increased in 10-d TO fetuses due to large increases in interairway distances; this resulted from a large increase in mesenchymal tissue. The interairway distances at 15 d of TO were reduced co mpared with the 10-d value but were still similar to 30% larger than contro l values. We conclude that TO at <90 d of gestation in fetal sheep induces a greater increase in lung tissue growth than later in gestation but also c auses fetal hydrops and produces changes in lung structure that are not com patible with efficient gas exchange. Thus, increased lung expansion at a si milar stage of development in human fetuses is unlikely to induce changes i n lung development that would facilitate gas exchange after birth.