HUMAN TROPHOBLAST - SENSITIVITY TO GLUCOSE AND OXYGEN DEPRIVATION

Abstract

Top of pageAbstract Trophoblast uses large amounts of glucose and oxygen to meet the energy requirements of its synthetic and transport functions. We studied the effects of glucose and oxygen shortage on energy metabolism in a highly enriched population of trophoblastic cells from normal placentae, obtained with collagenase digestion and density gradient centrifugation. Intracellular adenylate (ATP, ADP, AMP) pool was labeled with 14C-adenine. Metabolic integrity was monitored with the adenylate energy charge (EC). Glucose-free medium or 100% N2-atmosphere had no effect on EC. Inhibition of glycolysis with 2-deoxy-D-glucose (DG) caused a rapid reduction in adenylates to less than a fourth and EC to about 65% in both first and third trimester cultures. Inhibition of oxidative phosphorylation with rotenone (R) caused a slower reduction in EC (p<0.01) and in adenylates than DG in first trimester. The effect of R on EC was also less (p<0.01) in first than third trimester. R in the presence of glucose had no effect. Concl.: 1) the trophoblast is able to maintain its energy supply by glycolysis or respiration alone, 2) inhibition of ATP-production causes a profound deterioration in energy status, 3) exogenous glucose is required for glycolytic ATP-production, 4) susceptibility to hypoxia increases as a function of gestational age.