Alterations in lung expansion affect surfactant protein A, B, and C mRNA levels in fetal sheep

Obstruction of the fetal trachea is a potent stimulus for fetal lung growth , and it has been suggested that this procedure may be used therapeutically to reverse lung growth deficits in human fetuses with lung hypoplasia. How ever little is known about the effects of increased lung expansion on other aspects of lung development. Our aim was to determine the effect of increa sed and decreased lung expansion on the mRNA levels encoding surfactant pro tein (SP) A, SP-B, and SP-C in ovine fetal lungs. Lung tissue samples were collected from fetuses exposed to 2, 4, or 10 days of increased lung expans ion caused by tracheal obstruction. The mRNA levels for SP-A, SP-B, and SP- C: were determined by Northern blot analysis with specific ovine cDNA probe s; SP-A protein levels were determined by Western blot analysis. Compared w ith age-matched (128-day gestational age) control fetuses, SP-A, SP-B, and SP-C mRNA levels in fetal lung tissue were significantly reduced at 2 days of tracheal obstruction and remained reduced at 4 and 10 days. However, SP- A protein levels were not reduced at 2 days of tracheal obstruction, tended to be reduced at 4 days, and were almost undetectable at 10 days. In contr ast to tracheal obstruction, 7 days of lung liquid drainage significantly i ncreased SP-C, but not SP-A, mRNA levels in fetal lung tissue compared with age-matched control fetuses. Our results demonstrate that increases in fet al lung expansion, induced by obstruction of the fetal trachea, cause large simultaneous reductions in SP-A, SP-B, and SP-C mRNA levels in the fetal l ung as well as a decrease in SP-A protein levels, These data suggest that e xpression of the genes encoding SPs in the fetal lung are specifically resp onsive to the degree of lung expansion.