INFLUENCE OF GLUCOSE AND INSULIN OF PROSTACYCLIN SYNTHESIS IN CULTURED TR0PH0BLAST CELLS

It is known that placental cells can produce prostacyclin /PGI2/. At present, the physiological role of trophoblast PGI2 production can only be speculative. PGI2 produced by trophoblast may help to prevent the platelet aggregation and thrombosis in spiral arteries and it can also explain the maintance of, and blood flow through, the spiral arteries during endovascular trophoblast invasion in early pregnancy. It has been previously shown that increased glucose concentrations in the incubation fluid can inhibit the formation of PGI2 by rat aortic rings. The aim of present investigation was to study the effect of glucose and insulin on the generation of PGI? by trophoblast obtained from early pregnancy. Trophoblast tissue was obtained immediately from surgical termination of first trimester pregnancy /9 specimens/. Trophoblast was cultured using the method of Jogee et al. Cells obtained from trypsinizaticn were cultured at a density of 2×105 cells/ml in medium 199 containing 10% horse,serum. Glucose /5.5, 16.5 and 33mmol/l / and insulin /103 , 104 and 106 mU/1 / were added to culture and the effect on 6-oxo-PGF2 production over a 24-hr incubation was assessed. Control cultures were incubated without glucose and insulin. The concentration of 6-oxo-PGF2 in culture supernatans were measured by specific radioimmunoassay /3H-6-oxo-PGF1, RIA-kit, New England Nuclear, USA /.There was a significant decrease in 6-keto-PGF10c production by trophoblast cells incubated with increased glucose concentrations /16.5 and 33 mmol/1 / compared to controls / p<0.001/. In contrast, insulin in growth medium did not have any effects on the PGI production. These data suggest that high concentrations of 2 glucose inhibit PGIp production by cultured trophoblast cells. This decreased PGIp synthesis may impair the blood supply of trophoblast which could play a role in the development of congenital anomalies in pregnant women with poorly controlled diabetes mellitus in the first trimester of pregnancy.