Epidermal growth factor and lung development in the offspring of the diabetic rat

Fetuses of diabetic mothers who were exposed to excessive glucose show dela yed maturation. Under these conditions, altered growth factor expression or signaling may have important regulatory influences. We examined the role o f epidermal growth factor (EGF) in lung development and maternal diabetes i n the rat. In order to evaluate the possible role of glucose for the expres sion of EGF and the growth of lung tissue, we performed in vitro studies wi th organotypic cultures of fetal alveolar cells obtained from control rats. Compared to pups of normal rats, the newborn rats of untreated diabetic rat s had reduced body weight, but normal lung weight relative to body weight. The air:mesenchyme ratio and the average size of alveoli per mm(2) lung tis sue were reduced. The immunoreactivity (IR) of EGF, which was quantified us ing a computerized image analysis system, appeared with increased intensity and was associated with a reduced intensity of surfactant protein A-IR. Th e only difference observed between pups of treated diabetic rats and contro ls was a decrease in the lung weight:body weight ratio. In organotypic cult ures, the presence of 13 mmol/L glucose in the cell media increased immunor eactive staining against EGF, but decreased the incorporation of thymidine as compared to the results obtained with alveolar cells grown in a normophy siological concentration of glucose (3 mmol/L). Addition of EGF increased t he thymidine incorporation only in cells grown in 3 mM glucose. These findings may indicate immaturity of the lungs of pups of untreated di abetic rats, and subtle alterations in the lungs of pups from treated diabe tic rats. The results also suggest that glucose plays a role in the express ion of EGF, and that cells exposed to high concentrations of glucose are le ss responsive to EGF. Pediatr Pulmonol. 2000; 29:103-112. (C) 2000 Wiley-Li ss, Inc.