Effect of Hypoxia, Oxidative Stress and Lipopolysaccharides on the Release of Prostaglandins and Cytokines from Human Term Placental Explants

• Published in: Placenta (Eastbourne) Vol. 22; pp. S45 - S50
• Main Authors: Malek, A., Sager, R., Schneider, H.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford Elsevier Ltd 01-04-2001; Elsevier
• Subjects: Adult; Biological and medical sciences; Cell Hypoxia - drug effects; Cell Hypoxia - physiology; Chorionic Villi - drug effects; Chorionic Villi - metabolism; Culture Techniques; Cyclooxygenase Inhibitors - pharmacology; Cytokines - biosynthesis; Diseases of mother, fetus and pregnancy; Drug Interactions; Enzyme-Linked Immunosorbent Assay; Female; Gynecology. Andrology. Obstetrics; Humans; Hypoxia - complications; Indomethacin - pharmacology; Lipopolysaccharides - pharmacology; Medical sciences; Nitrobenzenes - pharmacology; Oxidative Stress; Oxygen - administration & dosage; Pregnancy; Pregnancy. Fetus. Placenta; Prostaglandins - biosynthesis; Sulfonamides - pharmacology; Xanthine - pharmacology; Xanthine Oxidase - pharmacology; Human; Oxidative stress; Oxygen; Pregnancy disorders; Prostaglandin; Fetal membrane; Enzyme; Arachidonic acid derivatives; Interleukin; Cytokine; Xanthine; Pregnancy toxemia; Placenta; Eicosanoid; Preeclampsia; Lipopolysaccharide; Female; Hypoxia; Xanthine oxidase; Oxidoreductases; Tumor necrosis factor α
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1053/plac.2001.0635

Placental hypoxia, ischaemia, reperfusion and resultant oxidative stress, with the release of various factors into the maternal vasculature acting as mediators of endothelial cell dysfunction, play an important role in the development of pre-eclampsia.
Human term placental tissue explants were exposed to different stressors, e.g. hypoxia, oxidative stress and lipopolysaccarides, and the effect on the release of prostanoids and cytokines was determined. The hypoxic environment consisted of 2 per cent O
2, 5 per cent CO
2and 93 per cent N
2. Oxidative stress was induced by addition of xanthine together with xanthine oxidase to the incubation medium. As a third experimental variable, lipopolysaccharide was added to the medium. Prostaglandins (8-iso-PGF
2α, or 6-keto-PGF
1αand TXB
2as stable metabolites of prostacyclin and thromboxane, respectively) and cytokines (TNF-α, IL-1α, IL-1β, IL-6) were measured using commercial ELISA assays.
Under control conditions, the production of prostaglandins in ng/24
h (mean±s.d.) was 6±3 for 8-iso-PGF
2α, 19±9 for 6-keto-PGF
1αand 5±2 for TXB
2. The production of cytokines was 13±6
pg for TNF-α, 7±2
pg for IL-1α, 5±3
pg for IL-1β and 18±9
ng for IL-6. Under hypoxia the production of prostaglandins remained unchanged and of the cytokines only IL-1β showed a 15-fold increase. Oxidative stress resulted in an increase in the release of prostaglandins and of cytokines of 4- to 15- and 3- to 130-fold, respectively. Lipopolysaccharides and oxidative stress had a similar effect on the production of prostaglandins, whereas the stimulatory effect of lipopolysaccharides on cytokines was significantly higher than that of oxidative stress.