Prostacyclin production by human placental cells in short-term culture

Human placentae of varying gestational ages have been cultured in vitro with little variation in cell type and pattern of growth found. Cell types found are similar morphologically and histochemically to those previously described. The biological specificity of the cells in culture was also confirmed by human placental lactogen production. Placental cells in culture appear to synthesize and release PGI₂ which can be identified by gas chromatography-mass spectrometry. Production of PGI₂ was routinely measured by radioimmunoassay (RIA) for 6-oxo-PGF_1α and 13,14-dihydro-6,15-dioxo-PGF_1α in culture supernatants. Good agreement was found between RIA and gas chromatography-mass spectrometry measurements. PGI₂ production in culture was not affected by mode of delivery, and synthetic capability was found to increase with gestational age. Production of PGI₂ by cell from preterm and term placentae was similar but significantly greater than that of first-trimester cells. As the proportion of PGI₂ produced in culture supernatants as 13,14-dihydro-6,15-dioxo-PGF_1α changed with time of incubation, it appears pertinent to measure this metabolite when assessing total PGI₂ production. Synthesis of PGI₂ was inhibited by the cyclo-oxygenase inhibitors indomethacin and aspirin and PGI₂ synthetase inhibitor 15 hydroperoxyarachidonic acid. However, in the culture system tranylcypromine, a putative specific inhibitor of PGI₂ synthetase, produced weak inhibition only before becoming cytotoxic. The cell culture system appears to offer a reliable and reproducible means for measuring placental PGI₂ production in vitro and in which to study factors controlling its production and metabolism.