Hypoxia attenuates PGE(2)but increases prostacyclin and thromboxane production in human term villous trophoblast.
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 E(2)(PGE(2)) thromboxane B(2)(TXB(2)), and prostacyclin (measured as 6-keto-PGF(1alpha)) by human term trophoblast cells and villous placental explants. Explants (n=8) and purified trophoblast cells (n=5) were 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 attentuated 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 versus the normoxic control, accompanied by increased production of 6-keto-PGF(1alpha)to 173.9+/-26.7 per cent after 48 h. TXB(2)production was increased to 172.3+/-25.9 per cent and 653.2+/-135.7 per cent (P< 0.05) control after 48 and 72 h of hypoxia, respectively. These results were confirmed in villous explants (n=3) cultured in the presence of exogenous 10 microm arachidonic acid. Hypoxia had no significant effect on TXB(2)and 6-keto-PGF(1alpha)in 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.
Blumenstein
M
M
Liggins Institute and Division of Pharmacology, The University of Auckland, Faculty of Medical and Health Sciences, 85 Park Road, Grafton, Auckland, New Zealand. nblumenstein@auckland.ac.nz
Keelan
J A
JA
Mitchell
M D
MD
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007700:Kinetics; D010100:Oxygen / Q000008:administration & dosage; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D013928:Thromboxane A2 / Q000096:biosynthesis*; D014327:Trophoblasts / Q000378:metabolism*
D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone; D010100:Oxygen