The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

Zivanit Ergaz, Dana Shoshani-Dror, Claire Guillemin, Meytal Neeman-azulay, Liza Fudim, Sarah Weksler-Zangen, Christopher J. Stodgell, Richard K. Miller, Asher Ornoy

Research output: Contribution to journalArticlepeer-review


High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1. ppm or 2. ppm of copper throughout their pregnancy. Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1. ppm and 2. ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 α among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity.

Original languageEnglish
Pages (from-to)209-220
Number of pages12
JournalToxicology and Applied Pharmacology
Issue number2
StatePublished - 1 Dec 2012
Externally publishedYes


  • CDr
  • CDs
  • Copper deficiency
  • Diabetes
  • FGR
  • Fetal growth restriction
  • Fetal resorption
  • HSD
  • Oxidative stress
  • PGD
  • RD
  • Rats

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology


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