STIMULATION BY HUMAN CHORIONIC-GONADOTROPIN OF PROSTAGLANDIN SYNTHESIS BY EARLY HUMAN PLACENTAL TISSUE

Successful establishment of pregnancy is dependent on inhibition of clotting and suppression of the maternal immune response at the feto-maternal interface. Early human placental production of prostacyclin (PGI2) and prostaglandin E2 (PGE2) may be important in this process. To examine the possible role of these PGs, we studied PGE and 6-keto-PGF1-alpha (stable metabolite of PGI2) synthesis in human placental (9-17 weeks gestation) organ cultures, and monolayer cultures of purified trophoblasts. PGE2 appeared to be the major prostanoid formed. Other arachidonic acid metabolites identified in placental organ culture were 6-keto-PGF1-alpha, thromboxane B2, PGF2-alpha, leukotriene B4, 5(S)-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, and 15-HETE. The synthesis of PGE and 6-keto-PGF1-alpha altered with gestation and was maximal in the younger placentas. Arachidonic acid (33-mu-M) stimulated and indomethacin (28-mu-M) inhibited PG production. hCG, including physiological concentrations, stimulated PGE and 6-keto-PGF1-alpha synthesis in placental organ cultures. This effect was most striking in the 9-12 week placentas, compared to 15-17 week placentas. A similar hCG-induced stimulation of PGE production occurred in monolayer cultures of trophoblasts. The addition of TSH, FSH, and LH indicated that this effect was specific for hCG. These data suggest that hCG may have a biological role in regulation of PG synthesis in early human placenta.