Hypoxia attenuates PGE(2) but increases prostacyclin and thromboxane production in human term villous trophoblast

Prostanoids hale been proposed to play a major role in the regulation of ut eroplacental blood flow. We examined the effect of hypoxia on the productio n of prostaglandin E-2 (PGE(2)) thromboxane B-2 (TXB2), and prostacyclin (m easured as 6-keto-PGF(1 alpha)) by human term trophoblast cells and villous placental explants. Explants (n=8) and purified trophoblast cells (n=5) we re incubated for 24-72 h under either normoxic (21 per cent O-2) or hypoxic (2 per cent O-2) conditions. In trophoblast monolayer cultures, hypoxia at tentuated PGE(2) production rates to 52 +/- 9.4 per cent (mean +/- SEM, P < 0.05) but recovered to control rates within 48 h. In villous explants, PGE( 2) production was significantly decreased after 48 and 72 h of hypoxia vers us the normoxic control, accompanied by increased production of 6-keto-PGF( 1 alpha) to 173.9 +/- 26.7 per cent after 48 h. TXB2 production mas increas ed to 172.3 +/- 25.9 per cent and 653.2 +/- 135.7 per cent (P <0.05) contro l after 48 and 72 h of hypoxia, respectively. These results were confirmed in villous explants (n=3) cultured in the presence of exogenous 10 muM arac hidonic acid. Hypoxia had no significant effect on TXB2 and 6-keto-PGF(1 al pha) in trophoblast cells. In summary, our findings suggest that hypoxia co uld be responsible for abnormal profiles of prostanoid production commonly observed in women with pre-eclampsia. These results indicate a putative lin k between hypoxia and compromised placental perfusion. (C) 2001 Harcourt Pu blishers Ltd.