Hypoxia Attenuates PGE2but Increases Prostacyclin and Thromboxane Production in Human Term Villous Trophoblast

Abstract

Prostanoids have been proposed to play a major role in the regulation of uteroplacental blood flow. We examined the effect of hypoxia on the production of prostaglandin E2(PGE2) thromboxane B2(TXB2), and prostacyclin (measured as 6-keto-PGF1α) by human term trophoblast cells and villous placental explants. Explants (n=8) and purified trophoblast cells (n=5) were incubated for 24–72h under either normoxic (21 per cent O2) or hypoxic (2 per cent O2) conditions. In trophoblast monolayer cultures, hypoxia attentuated PGE2production rates to 52±9.4 per cent (mean±sem, P< 0.05) but recovered to control rates within 48h. In villous explants, PGE2production was significantly decreased after 48 and 72h of hypoxia versus the normoxic control, accompanied by increased production of 6-keto-PGF1αto 173.9±26.7 per cent after 48h. TXB2production was increased to 172.3±25.9 per cent and 653.2±135.7 per cent (P< 0.05) control after 48 and 72h of hypoxia, respectively. These results were confirmed in villous explants (n=3) cultured in the presence of exogenous 10μm arachidonic acid. Hypoxia had no significant effect on TXB2and 6-keto-PGF1αin trophoblast cells. In summary, our findings suggest that hypoxia could be responsible for abnormal profiles of prostanoid production commonly observed in women with pre-eclampsia. These results indicate a putative link between hypoxia and compromised placental perfusion.