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Effects of Hypoxia on Regulation of Prostanoid Production in Decidual Endothelial Cells in Normal and Preeclamptic Pregnancy

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Abstract

Objectives

To examine the effect on prostacyclin and thromboxane prodution of incubating decidual endothelial cells under hypoxic conditions, comparing cells from normal and preeclamptic pregnancies. Furthermore, to determine whether hypoxia is deleterious to cell growth, and test the effect of stimulation and inhibition on prostanoid production.

Methods

Decidual endothelial cells were exposed for a total of 40 hours to normoxic (20% O2) or hypoxic (2% O2) conditions. Prostacyclin and thromboxane secretion over the final 24 hours of incubation was measured and cell numbers after incubation determined. Lipopolysaccharide (LPS) (1.0 μg/mL) was used as a stimulator and pirmagrel (1.0 μmol/L) and tranylcypromine (10.0 μmol/L) as prostanoid synthase inhibitors.

Results

Incubations in hypoxia resuulted in increased thromboxane (P < .05) but no change in prostacyclin production. This thromboxane increase was abrogated by pirmagrel. LPS caused significant stimulation of prostacyclin and thromboxane secretion and both LPS and hypoxia resulted in lower cell numbers. Decidual endothelial cells from normal and preeclamptic pregnancies were generally not different.

Conclusions

This study indicates that in preeclampsia, where decidual endothelial cells are in a relatively more hypoxic environment, thromboxane production by these cells is likely to be increased and the prostacyclin/thromboxane ratio decreased. The thromboxane synthase inhibitor, pirmagrel, was able to reverse this abnormal increased secretion of thromboxane in vitro.

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Correspondence to Eileen D. M. Gallery MD.

Additional information

Supported by research grants from the Baxter Extramural Grant Program and the Australian Kidney Foundation and The National Health and Medical Research Council of Australia.

The authors are grateful to Sister Mei Ling Chang and the consultant obstetricians and their registrars at Royal North Shore Hospital for assistance in sample collection. Thanks are also due to Melinda Hader for technical assistance.

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Rowe, J., Campbell, S. & Gallery, E.D.M. Effects of Hypoxia on Regulation of Prostanoid Production in Decidual Endothelial Cells in Normal and Preeclamptic Pregnancy. Reprod. Sci. 7, 118–124 (2000). https://doi.org/10.1177/107155760000700207

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