Effect of high glucose on fetal lung maturation at different times in gestation.
Hyperglycemia has been implicated as a cause of delayed fetal lung maturation in the diabetic pregnancy. It has been previously demonstrated that high glucose levels inhibit biochemical and morphological maturation of fetal rat lung in vitro. To explore whether there is a critical period for maximal effects of high glucose, fetal rat lung explants from day 18-22 (term) were examined after culture for 44 h in media containing 10 or 100 mM glucose. Rate of choline incorporation into PC and DSPC was significantly decreased in explants derived from day 20-22 fetuses after culture with high glucose. Paradoxically, in explants derived from day 18-19 fetuses choline incorporation rate was increased. Significant decreases in total PC and DSPC were seen in the high glucose group on days 20-21; however, earlier in gestation no differences in PC and DSPC were noted, despite the higher rate of choline incorporation into PC and DSPC, suggesting an increased turnover rate. High glucose levels also resulted in significantly decreased incorporation of labeled glycerol and palmitate into PC. Morphologic analysis of right upper lobe explants revealed significant decreases in the number of type II pneumocytes and lamellar bodies per alveolar lining cell in high glucose treated explants derived from days 19-20, but not before or after that time in gestation. Prior to day 20 there were few luminal lamellar bodies in potential airspaces. By day 20, the high glucose group had significantly fewer luminal lamellar bodies, although by day 21 the difference was no longer significant. These results suggest that high glucose may have a greater inhibitory effect late in gestation and that there may be critical periods in lung development when differences in substrate availability and utilization have differing effects.
Gewolb
I H
IH
Department of Pediatrics, University of Maryland School of Medicine, Baltimore 21201, USA.
D000818:Animals; D003470:Culture Media; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects; D005865:Gestational Age; D005947:Glucose / Q000494:pharmacology*; D006943:Hyperglycemia / Q000139:chemically induced / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D003470:Culture Media; D010743:Phospholipids; D005947:Glucose