The effects of tracheal occlusion and release on type II pneumocytes in fetal lambs

Fetal tracheal occlusion (TO) has been shown to lead to lung hyperplasia in various animal models, and this procedure has already been carried out in human fetuses with congenital diaphragmatic hernia (CDH). However, the authors previously showed that TO caused a decrease in type II pneumocytes.

The aim of this study is to examine the effects of TO and release on type II pneumocytes.

To was carried out with a Swan Ganz or Fogarty catheter in fetal sheep at 116 to 118 days of gestation. TO was maintained for 2 weeks followed by deflation of the balloon for 1 week before delivery, in group 1; in group 2, TO was maintained for 19 days and released 2 days before delivery. Group 3 consisted of previously reported animals who had TO maintained until birth. Unoperated twins served as controls. All specimens were analyzed using the surfactant protein C (SP-C) mRNA as a specific marker for type II pneumocytes. We used Northern Blot and in situ hybridization techniques to quantify total SP-C and the density of type II cells. Electron microscopy (EM) was also used to evaluate and quantitate type II cells.

TO resulted in significant lung growth in all groups. In situ hybridization and Northern Blot analysis showed that there was a complete recovery of type II cells in group 1 versus controls. Quantitative EM analysis confirmed these findings. In group 2 the number of type II cells was decreased but there was an increase in SP-C content per type II cell versus group 3.

Lung growth after TO appears to occur at the expense of type II cell differentiation. This effect is reversible with the release of TO before birth in this animal model.