Tumor necrosis factor-α alters maternal and embryonic zinc metabolism and is developmentally toxic in mice

M. W. Taubeneck, G. P. Daston, J. M. Rogers, M. Eric Gershwin, A. Ansari, Carl L Keen

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

We tested the hypothesis that tumor necrosis factor-α (TNF-α) would be teratogenic in mice due in part to its effects on zinc metabolism. In Experiment 1, nonpregnant mice were injected with a single dose of TNF-α (40,000 U) or PBS and then received a 65Zn-labeled meal. Mice killed 10 h after TNF-α treatment had high liver 65Zn and low plasma 65Zn, compared with controls. In Experiment 2, gestation day 8 (GD 8) mice were injected with PBS or TNF-α and then received a 65Zn-labeled meal. Dams killed 10 h after TNF-α treatment had higher liver and kidney 65Zn and lower plasma and embryonic 65Zn accumulation than controls. In Experiment 3, TNF-α dosing from GD 7-12 was associated with high maternal liver Zn and metallothionein concentrations on GD 13 and a high frequency of exencephaly on GD 18. In Experiment 4, dams fed diets containing 4.5, 12.5 or 50.0 μg Zn/g were given PBS or TNF-α on GD 7-12. Gross fetal defects were not observed in the PBS-treated litters evaluated on GD 18. In contrast, TNF-α- treated litters were characterized by multiple defects, with the incidence and severity being highest in the low Zn diet group. In Experiment 5, embryos cultured in serum from TNF-α-treated animals exhibited a high frequency of defects; the developmental toxicity of this serum was ameliorated when it was supplemented with Zn. Thus, the developmental toxicity of TNF-α is due in part to its influence on Zn metabolism.

Original languageEnglish (US)
Pages (from-to)908-919
Number of pages12
JournalJournal of Nutrition
Volume125
Issue number4
StatePublished - 1995

    Fingerprint

Keywords

  • development
  • metallothionein
  • mice
  • tumor necrosis factor-α
  • zinc

ASJC Scopus subject areas

  • Food Science
  • Medicine (miscellaneous)

Cite this

Taubeneck, M. W., Daston, G. P., Rogers, J. M., Gershwin, M. E., Ansari, A., & Keen, C. L. (1995). Tumor necrosis factor-α alters maternal and embryonic zinc metabolism and is developmentally toxic in mice. Journal of Nutrition, 125(4), 908-919.