The effect of maternal iron deficiency on zinc and copper levels and on genes of zinc and copper metabolism during pregnancy in the rat

Br J Nutr. 2019 Jan;121(2):121-129. doi: 10.1017/S0007114518003069. Epub 2018 Nov 28.

Abstract

Fe deficiency is relatively common in pregnancy and has both short- and long-term consequences. However, little is known about the effect on the metabolism of other micronutrients. A total of fifty-four female rats were fed control (50 mg Fe/kg) or Fe-deficient diets (7·5 mg/kg) before and during pregnancy. Maternal liver, placenta and fetal liver were collected at day 21 of pregnancy for Cu and Zn analysis and to measure expression of the major genes of Cu and Zn metabolism. Cu levels increased in the maternal liver (P=0·002) and placenta (P=0·018) of Fe-deficient rats. Zn increased (P<0·0001) and Cu decreased (P=0·006) in the fetal liver. Hepatic expression of the Cu chaperones antioxidant 1 Cu chaperone (P=0·042) and cytochrome c oxidase Cu chaperone (COX17, P=0·020) decreased in the Fe-deficient dams, while the expression of the genes of Zn metabolism was unaltered. In the placenta, Fe deficiency reduced the expression of the chaperone for superoxide dismutase 1, Cu chaperone for superoxide dismutase (P=0·030), ceruloplasmin (P=0·042) and Zn transport genes, ZRT/IRT-like protein 4 (ZIP4, P=0·047) and Zn transporter 1 (ZnT1, P=0·012). In fetal liver, Fe deficiency increased COX17 (P=0·020), ZRT/IRT-like protein 14 (P=0·036) and ZnT1 (P=0·0003) and decreased ZIP4 (P=0·004). The results demonstrate that Fe deficiency during pregnancy has opposite effects on Cu and Zn levels in the fetal liver. This may, in turn, alter metabolism of these nutrients, with consequences for development in the fetus and the neonate.

Keywords: ATOX1 antioxidant 1 copper chaperone; CCS copper chaperone for superoxide dismutase; COX17 cytochrome c oxidase copper chaperone; CP ceruloplasmin; ZIP ZRT/IRT-like protein; ZnT zinc transporter; Copper; Iron status; Liver; Placenta; Pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cation Transport Proteins
  • Ceruloplasmin
  • Copper / analysis
  • Copper / metabolism*
  • Electron Transport Complex IV / genetics
  • Female
  • Fetus / metabolism
  • Gene Expression / physiology
  • Iron Deficiencies*
  • Liver / chemistry
  • Liver / embryology
  • Liver / metabolism
  • Maternal Nutritional Physiological Phenomena
  • Molecular Chaperones
  • Placenta / chemistry
  • Placenta / metabolism
  • Pregnancy
  • Rats
  • Zinc / analysis
  • Zinc / metabolism*

Substances

  • Cation Transport Proteins
  • Ccs protein, rat
  • Molecular Chaperones
  • Slc39a4 protein, rat
  • Slc30a1 protein, rat
  • Copper
  • Ceruloplasmin
  • Electron Transport Complex IV
  • Zinc