Author:
Kilani R T,Mackova M,Davidge S T,Winkler-Lowen B,Demianczuk N,Guilbert L J
Abstract
Tumor necrosis factor α (TNFα) has been implicated in the abnormally high levels of trophoblast apoptosis seen in placentae from pregnancies complicated by small births. We examined the hypothesis that at physiological (35–50 mmHg) oxygen tensions, the production of TNFα stimulates the apoptosis of placental trophoblasts associated with infants that are intrauterine growth-restricted (IUGR). Highly purified cytotrophoblasts (CT) from IUGR-complicated pregnancies spontaneously underwent a higher rate of apoptosis after 24 h of culture at a normoxic (for villous CT) tension of 38 mmHg than did CT from normal placentae. Real-time PCR analysis of TNFαmRNA revealed ~threefold higher levels in IUGR trophoblasts afterculturing at a pO2of 38 mmHg. A higher level of TNFα receptor p55 (which mediates apoptosis) was found in IUGR CT by western blot analysis at pO2of <10, 38, and 140 mmHg. Neutralizing antibody to TNFα significantly inhibited the apoptosis of IUGR trophoblasts cultured at 38 mmHg and addition of TNFα significantly elevated apoptosis of normal and IUGR trophoblasts but less in IUGR cells cultured at <10 mmHg. We conclude that at physiological oxygen tensions (38 mmHg), villous CT from IUGR pregnancies, when compared with uncomplicated pregnancies, undergo more TNFα-induced apoptosis both because of elevated expression of TNFα and TNF receptor p55.
Subject
Cell Biology,Obstetrics and Gynaecology,Endocrinology,Embryology,Reproductive Medicine
Cited by
36 articles.
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