There is evidence that lung distension may influence pulmonary epithelial differentiation. Previous studies have suggested that increased distension of fetal lung in vivo reduces formation of type II cells and decreased distension has the opposite effect. Prolonged stretch of isolated type II cells increases expression of a specific pulmonary epithelial type I cell protein (rTI40). Immuno-histochemical studies indicate that rTI40 is localized to the apical plasma membrane of type I cells.

We investigated the effects of oligohydramnios (OH), which has been shown to decrease distension of the fetal lung, on pulmonary development in fetal rats. We produced OH at 15 or 16 d gestation in all fetuses in one uterine horn by puncturing the uterine wall and fetal membranes of each fetal sac with a 22 gauge needle. Control fetuses (C) were littermates at corresponding positions in the opposite uterine horn. At 21 or 22 d, the fetuses were delivered under anesthesia, pithed and weighed. Lungs were weighed and frozen for later analysis. Compared to C fetuses, OH retarded fetal growth and caused pulmonary hypoplasia, based on measurements of lung weight (absolute weight and% of body weight) and content of DNA and protein; all changes were statistically significant for fetuses delivered at either 21 or 22 d. To assess effects of OH on pulmonary epithelial development, we measured the content of rTI40 in fetal lungs by semiquantitative immuno-dot blot. For fetuses delivered at 21 d (n=15 pairs), lung content of rTI40 was similar in OH and C fetuses (P=0.922). However, for those delivered at 22d (n=19 pairs), OH caused a decrease in rTI40 to 64% of C (P<0.001).

We conclude that mechanical factors (i.e., decreased lung distension) can influence differentiation of the distal pulmonary epithelium in fetal rats in late gestation. The decrease in rTI40 with OH may be due to(a) increased formation of type II cells with a corresponding relative decrease in type I cells, (b) reduced surface area of distal potential airspaces as a result of OH, or (c) decreased production of rTI40.

Supported by National Heart, Lung and Blood Institute Grant HL-24075.