Role of Myo-inositol in Impairment of Fetal Lung Phosphatidylglycerol Biosynthesis in the Diabetic Pregnancy: Physiological Consequences of a Phosphatidylglycerol-deficient Surfactant in the Newborn Rat

Abstract

To test the hypothesis that the deficit of fetal lung surfactant phosphatidylglycerol (PG) in diabetic pregnancies was due to increased plasma myo-inositol, lung PG content and plasma myo-inositol level were compared in fetuses of streptozotocin-diabetic rats and in fetuses of rats injected with myo-inositol during the 4 last gestational days. An inverse linear correlation was established between circulating myo-inositol and lung phosphatidylglycerol content, including data from fetuses of diabetic rats, which is consistent with the hypothesis. Changes in phospholipid synthetic rates were estimated in fetuses of rats given myo-inositol by measuring incorporation of labelled glycerol on a six hour period on the 21st gestational day, after i.v. injection to the mother. Incorporation into PG was 2.5 times smaller but incorporation into PI or PC were not modified. Pulmonary function in PG-deficient newborns of rats given a high-dosage myo-inositol was assessed by pressure/volume measurements on the lung in situ and by measurement of oxygen tension in aortic blood. Opening pressure of alveoli for lung inflation was increased and blood oxygenation was reduced (30%) in newborns with PG-deficient surfactant as compared with controls, thus suggesting an important physiological role for surfactant PG at birth.