High glucose inhibits maturation of the fetal lung in vitro. Morphometric analysis of lamellar bodies and fibroblast lipid inclusions.

BACKGROUND

High glucose levels inhibit fetal lung maturation in vitro, consistent with the increased incidence of respiratory distress syndrome in diabetic gestation. Lung fibroblast neutral lipid stores may preferentially provide substrate to type II cells for surfactant phospholipid synthesis.

EXPERIMENTAL DESIGN

To analyze the impact of high glucose on fetal lung morphology and on fibroblast neutral lipid stores, 20-day fetal rat right upper lobe lung explants were cultured in F-12 medium with final glucose concentrations of 10 mM or 100 mM and were examined by electron microscopy.

RESULTS

Decreased numbers of type II pneumocytes/alveolar lining cell (0.19 +/- 0.04 versus 0.34 +/- 0.04; p < 0.05) and lamellar bodies/alveolar lining cell (0.48 +/- 0.13 versus 0.97 +/- 0.14; p < 0.05) were noted in the high glucose-treated explants. Lamellar bodies in potential airspaces were also significantly decreased in the high glucose group. Type II cell glycogen stores were increased in the glucose-treated group. The ratio of lamellar bodies in type II cells to lipid inclusions in adjacent fibroblasts was decreased in glucose-treated explants (0.23 +/- 0.09 versus 0.93 +/- 0.33 in controls; p < 0.01) as was the ratio of the total areal density of lamellar bodies to lipid inclusions in adjacent fibroblasts (2.78 +/- 0.24 versus 4.44 +/- 0.58; p < 0.01). Although the number of lipid inclusions/fibroblast and of fibroblasts/alveolar lining cell did not differ between the two groups, the size of fibroblast lipid inclusions was significantly greater in the high glucose-treated lungs (0.79 +/- 0.12 versus 0.45 +/- 0.04 microM 2; p < 0.02), resulting from a subpopulation of large lipid inclusions measuring > 1 microM 2.

CONCLUSIONS

These data confirm our previous biochemical results indicating an adverse effect of high glucose on fetal lung surfactant metabolism in vitro and are suggestive of a block in the trafficking of lipids from fibroblasts to type II cells under these conditions. This block may be involved in the pathogenesis of the delay in fetal lung development observed in the diabetic pregnancy.