Effect of prolonged gestation on placental and maternal liver enzyme activities in the rat

Prolongation of gestation in rats up to 26 days, was produced by a single i.v. administration of human chorionic gonadotropin on day 18 of pregnancy, and its effect on placental and maternal liver enzymes of regulatory importance for glycolysis, glycogen metabolism, NADPH generation, gluconeogenesis and lipogenesis was determined. The chorionic gonadotropin-induced postmaturity resulted in continued placental and fetal growth. However the activity of all the investigated placental enzymes gradually decreased on day 26 of gestation from 42% (pyruvate kinase) to 82% (acetyl-CoA carboxylase) as compared to day 21 of gestation. This decrease was a continuation of decline of placental enzyme activity during the course of normal gestation, as observed previously between day 15 and 20 of gestation. The decrease in the capacity of glycolysis was confirmed by measuring in vitro the conversion of labeled glucose to CO₂ and lactate, which fell from day 15 to 25 of gestation by 43%. The placental glycogen content decreased significantly after day 24 of gestation, coincidently with the decreases in the activity of glycogen synthetase phosphatase and phosphorylase activities. In the maternal liver there was a decrease in the activity of enzymes related to glycolysis and lipogenesis and an increase in the activity of enzymes related to gluconeogenesis. This was accompanied by a decrease in glycogen synthetase phosphatase activity and a rise in serum free fatty acids. The results indicate a general trend of decrease in the activity of placental enzymes of different mtabolic pathways upon prolongation of gestation. Particularly the fall in energy supply through glycolysis may underly the functional insufficiency of the placenta in postmaturity. The changes on the maternal side represent an accentuation of a trend developing during the late stage of normal gestation, a transition to fat utilization and gluconeogenesis together with a decrease in carbohydrate utilization and fatty acid synthesis.