Delayed Lung Maturation in the Macrosomic Offspring of Genetically Determined Diabetic (db/|[plus]|) Mice1

摘要

We studied a genetically determined diabetes in pregnancy, the heterozygous diabetes (db/+) mouse. We found that fetal mice from these pregnancies are macrosomic with increased body, lung, and placenta wt, have altered organ protein, DNA and phospholipid content, and exhibit abnormal carbohydrate metabolism with increased liver and glycogen content. We further studied the effect of increased substrate availability and utilization on lung growth and maturation in (db/+) fetal mice, by measuring lung phospholipid synthesis as represented by the incorporation of the radiolabeled precursors, [3H]choline and [14C]glycerol, in fetal lung at 18 days’ gestation (term=19). Diabetic fetuses incorporated significantly more [3H]- choline into disaturated phosphatidylcholine than controls (1.32 ± 0.10 x 10-2 versus 0.78 ± 0.05 x 10-2 nmol/g protein/min, mean ± SE; p14C]glycerol into phosphatidylglycerol than controls (3.18 ± 0.38 versus 4.91 ± 0.53 nmol/g protein/min, mean ± SE;pversus 3.17 ± 0.14; mean ± SE; pversus 0.43 ± 0.02, mean ± SE; pversus 0.66 ± 0.03, mean ± SE; p<0.01). The increased synthesis of lung disaturated phosphatidylcholine in diabetic fetal mice may reflect the enhancement of body and lung growth in these macrosomic fetuses. Lung maturation, as represented by phosphatidylglycerol synthesis, the phosphatidylglycerol/phosphatidylinositol ratio, and morphologic indices, was abnormal in diabetic fetuses. The diabetic mouse is a useful model for studying the mechanisms resulting in enhanced growth and concomitant alterations in lung maturation in the infant of a diabetic mother.