Biochemical Journal

Research article

Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro

Lorraine GAMBLING, Ruth DANZEISEN, Susan GAIR, Richard G. LEA, Zehane CHARANIA, Nita SOLANKY, Kavita D. JOORY, S. Kaila S. SRAI, Harry J. McARDLE


Maternal iron deficiency during pregnancy induces anaemia in the developing fetus; however, the severity tends to be less than in the mother. The mechanism underlying this resistance has not been determined. We have measured placental expression of proteins involved in iron transfer in pregnant rats given diets with decreasing levels of iron and examined the effect of iron deficiency on iron transfer across BeWo cell layers, a model for placental iron transfer. Transferrin receptor expression was increased at both mRNA and protein levels. Similarly, expression of the iron-responsive element (IRE)-regulated form of the divalent metal transporter 1 (DMT1) was also increased. In contrast, the non-IRE regulated isoform showed no change in mRNA levels. Protein levels of DMT1 increased significantly. Iron efflux is thought to be mediated by the metal transporter protein, IREG1/ferroportin1/MTP1, and oxidation of Fe(II) to Fe(III) prior to incorporation into fetal transferrin is carried out by the placental copper oxidase. Expression of IREG1 was not altered by iron deficiency, whereas copper oxidase activity was increased. In BeWo cells made iron deficient by treatment with desferrioxamine (‘deferioxamine’), iron accumulation from iron-transferrin increased, in parallel with increased expression of the transferrin receptor. At the same time, iron efflux also increased, showing a higher flux of iron from the apical to the basolateral side. The data show that expression of placental proteins of iron transport are up-regulated in maternal iron deficiency, resulting in an increased efficiency of iron flux and a consequent minimization of the severity of fetal anaemia.

  • caeruloplasmin
  • divalent metal transporter 1
  • hephaestin
  • IREG1
  • placenta
  • transferrin receptor


  • Abbreviations used: IRE, iron-responsive element; DMT1, divalent metal transporter 1; BSS, balanced salt solution; DFO, desferrioxamine; GAPDH, glyceraldehyde-3-phosphate dehydrogenase.