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 synd rome in diabetic gestation. Lung fibroblast neutral lipid stores may p referentially provide substrate to type II cells for surfactant phosph olipid synthesis. EXPERIMENTAL DESIGN: To analyze the impact of high g lucose on fetal lung morphology and on fibroblast neutral lipid stores , 20-day fetal rat right upper lobe lung explants were cultured in F-1 2 medium with final glucose concentrations of 10 mM or 100 mM and were examined by electron microscopy. RESULTS: Decreased numbers of type I l 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 ve rsus 0.97 +/- 0.14; p < 0.05) were noted in the high glucose-treated e xplants. Lamellar bodies in potential airspaces were also significantl y decreased in the high glucose group. Type II cell glycogen stores we re increased in the glucose-treated group. The ratio of lamellar bodie s in type II cells to lipid inclusions in adjacent fibroblasts was dec reased 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 in clusions/fibroblast and of fibroblasts/alveolar lining cell did not di ffer between the two groups, the size of fibroblast lipid inclusions w as significantly greater in the high glucose-treated lungs (0.79 +/- 0 .12 versus 0.45 +/- 0.04 mu M(2); P < 0.02), resulting from a subpopul ation of large lipid inclusions measuring >1 mu M(2). CONCLUSIONS: The se data confirm our previous biochemical results indicating an adverse effect of high glucose on fetal lung surfactant metabolism in vitro a nd are suggestive of a block in the trafficking of lipids from fibrobl asts to type II cells under these conditions. This block may be involv ed in the pathogenesis of the delay in fetal lung development observed in the diabetic pregnancy.