Open AccessEndogenous tumor necrosis factor α mediates enhanced apoptosis of cultured villous trophoblasts from intrauterine growth-restricted placentae
Author(s) -
Ruhangiz T. Kilani,
Martina Macková,
Sandra T. Davidge,
Bonnie WinklerLowen,
Nestor Demianczuk,
Larry J. Guilbert
Publication year - 2007
Publication title -
reproduction
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.208
H-Index - 136
eISSN - 1741-7899
pISSN - 1470-1626
DOI - 10.1530/rep-06-0080
Subject(s) - apoptosis , tumor necrosis factor alpha , trophoblast , andrology , necrosis , endocrinology , medicine , biology , western blot , receptor , placenta , fetus , pregnancy , gene , biochemistry , genetics
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 pO 2 of 38 mmHg. A higher level of TNFα receptor p55 (which mediates apoptosis) was found in IUGR CT by western blot analysis at pO 2 of <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.