This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kilani, R T Articles by Guilbert, L J Search for Related Content PubMed PubMed Citation Articles by Kilani, R T Articles by Guilbert, L J

Endogenous tumor necrosis factor mediates enhanced apoptosis of cultured villous trophoblasts from intrauterine growth-restricted placentae

¹ University of Alberta Perinatal Research Centre, Edmonton, Canada, ² Departments of Medical Microbiology and Immunology and ³ Obstetrics and Gynaecology, University of Alberta, Edmonton, Canada

Correspondence should be addressed to L J Guilbert, 6-25 HMRC, 8440-112 Street, University of Alberta, Edmonton, Canada T6G 2S2; Email: larry.guilbert{at}ualberta.ca

Tumor necrosis factor (TNF) 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 TNF 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 TNFmRNA revealed ~threefold higher levels in IUGR trophoblasts afterculturing at a pO₂ of 38 mmHg. A higher level of TNF receptor p55 (which mediates apoptosis) was found in IUGR CT by western blot analysis at pO₂ of <10, 38, and 140 mmHg. Neutralizing antibody to TNF significantly inhibited the apoptosis of IUGR trophoblasts cultured at 38 mmHg and addition of TNF 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 TNF-induced apoptosis both because of elevated expression of TNF and TNF receptor p55.

This article has been cited by other articles:

				H. Kuang, Q. Chen, Y. Zhang, L. Zhang, H. Peng, L. Ning, Y. Cao, and E. Duan The Cytokine Gene CXCL14 Restricts Human Trophoblast Cell Invasion by Suppressing Gelatinase Activity Endocrinology, December 1, 2009; 150(12): 5596 - 5605. [Abstract] [Full Text] [PDF]

				D. D. Briana and A. Malamitsi-Puchner Reviews: Adipocytokines in Normal and Complicated Pregnancies Reproductive Sciences, October 1, 2009; 16(10): 921 - 937. [Abstract] [PDF]

				O. B. Christiansen, H. S. Nielsen, M. Lund, R. Steffensen, and K. Varming Mannose-binding lectin-2 genotypes and recurrent late pregnancy losses Hum. Reprod., February 1, 2009; 24(2): 291 - 299. [Abstract] [Full Text] [PDF]

				O M Faye-Petersen The placenta in preterm birth J. Clin. Pathol., December 1, 2008; 61(12): 1261 - 1275. [Abstract] [Full Text] [PDF]

				F. Stonek, E.-K. Bentz, E. Hafner, M. Metzenbauer, K. Philipp, L. A. Hefler, and C. B. Tempfer A Tumor Necrosis Factor {alpha} Promoter Polymorphism and Pregnancy Complications: Results of a Prospective Cohort Study in 1652 Pregnant Women Reproductive Sciences, July 1, 2007; 14(5): 425 - 429. [Abstract] [PDF]