Abnormal development and increased 3-nitrotyrosine in copper-deficient mouse embryos

Molly E. Beckers-Trapp, Louise Lanoue, Carl L Keen, Robert B. Rucker, Janet Y. Uriu-Adams

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Copper-deficient rat embryos are characterized by brain and heart anomalies, low superoxide dismutase activity, and high superoxide anion concentrations. One consequence of increased superoxide anions can be the formation of peroxynitrite, a strong biological oxidant. To investigate developmentally important features of copper deficiency, GD 8.5 mouse embryos from copper-adequate and copper-deficient dams were cultured in media that were adequate or deficient in copper. After 48 h, copper-deficient embryos exhibited brain and heart anomalies, and a high incidence of yolk sac vasculature abnormalities compared to controls. Immunohistochemistry of 4-hydroxynonenal and 8-hydroxy-2′-deoxyguanosine for lipid and DNA damage, respectively, was similar between groups. In contrast, 3-nitrotyrosine, taken as a measure of protein nitration, was markedly higher in the neuroepithelium of the anterior neural tube of copper-deficient embryos than in controls. Repletion of copper-deficient media with copper, or supplementation with copper-zinc superoxide dismutase, Tiron, or glutathione peroxidase did not ameliorate the abnormal development, but did decrease 3-nitrotyrosine in neuroepithelium of copper-deficient embryos. These data support the concept that while copper deficiency compromises oxidant defense and increases protein nitration, additional mechanisms, e.g., altered nitric oxide metabolism may contribute to copper-deficiency-induced teratogenesis.

Original languageEnglish (US)
Pages (from-to)35-44
Number of pages10
JournalFree Radical Biology and Medicine
Issue number1
StatePublished - Jan 1 2006


  • 3-Nitrotyrosine
  • 4-Hydroxynonenal
  • 8-Hydroxy-2′-deoxyguanosine
  • Copper deficiency
  • Embryo development
  • Free radicals
  • Oxidative stress
  • Superoxide dismutase
  • Yolk sac

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry


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