Evolution of CFTR protein distribution in lung tissue from normal and CF human fetuses.

In order to determine whether or not CFTR protein distribution differs between the airways of fetuses with Cystic Fibrosis (CF) from the airways of normal fetuses we studied the distribution pattern of the CFTR protein in lung. Cases of normal and CF human fetuses as well as cases of normal neonates were examinated. Our aim was to establish whether CFTR expression during pregnancy could be correlated with the maturation of the airways, and to compare normal and CF samples. We hypothesized that any difference between normal and CF fetal lung in CFTR protein expression could be related to a functional change appearing in early development even if no morphological differences could be detected at the light microscopic level. The distribution of CFTR protein progressively increased from 10 weeks of gestation (WG) to mid-gestation, but thereafter decreased until term. The CFTR protein was first detected in the cytoplasm of undifferentiated epithelial cells. Before mid-gestation, the immunostaining was strongly positive in bronchi, in sub-mucosal glands, and in lung parenchyma. Then, it became localized to the apical zone of the epithelial cells. This pattern correlated with differentiation during the second half of gestation. The main difference observed between normal and CF fetuses was a 3-week delay in detectability of the CFTR protein expression in the latter until 15 weeks of gestation. These results support the hypothesis of an early functional change. Abnormal fetal lung CFTR protein regulation could give rise to a predisposition to the post-natal inflammatory changes of the airways that characterize CF disease.