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Changes in the expression of intestinal iron transport and hepatic regulatory molecules explain the enhanced iron absorption associated with pregnancy in the rat
  1. K N Millard,
  2. D M Frazer,
  3. S J Wilkins,
  4. G J Anderson
  1. Iron Metabolism Laboratory, The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, Queensland 4029 Australia
  1. Correspondence to:
    Dr G J Anderson
    Iron Metabolism Laboratory, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia; gregAqimr.edu.au

Abstract

Background: Iron absorption increases during pregnancy to cater for the increased iron requirements of the growing fetus.

Aims: To investigate the role of the duodenal iron transport molecules and hepatic regulatory molecules in coordinating the changes in iron absorption observed during pregnancy.

Methods: Rats at various days of gestation and 24–48 hours post-partum were examined for hepatic expression of hepcidin, transferrin receptors 1 and 2, and HFE (the gene mutated in the most prevalent form of hereditary haemochromatosis), and duodenal expression of divalent metal transporter 1 (DMT1), duodenal cytochrome b (Dcytb), iron regulated mRNA (Ireg1), and hephaestin (Hp) by ribonuclease protection assay, western blotting, and immunohistochemistry.

Results: Decreased hepatic non-haem iron and transferrin saturation and increased expression of transferrin receptor 1 in the liver indicated a progressive reduction in maternal body iron stores during pregnancy. Duodenal expression of the iron transport molecules DMT1, Dcytb, and Ireg1 increased during pregnancy, and this corresponded with a reduction in hepcidin, HFE, and transferrin receptor 2 expression in the liver. Expression of all molecules returned towards control values by 24–48 hours post-partum.

Conclusions: These data indicate that increased expression of key iron transport molecules is responsible for the elevated iron absorption associated with pregnancy, and implicate hepcidin, HFE, and transferrin receptor 2 in determining how the maternal iron homeostatic machinery responds to the increased iron demands accompanying gestation.

  • duodenal cytochrome b
  • divalent metal transporter 1
  • hereditary haemochromatosis
  • iron regulation
  • Dcytb, duodenal cytochrome b
  • DMT1, divalent metal transporter 1
  • GAPDH, glyceraldehyde 3-phosphate dehydrogenase
  • HFE, the gene mutated in the most prevalent form of hereditary haemochromatosis
  • Hp, hephaestin
  • IRE, iron responsive element
  • Ireg1, iron regulated mRNA (also known as ferroportin 1)
  • NP, non-pregnant
  • PP, post-partum
  • RPA, ribonuclease protection assay
  • TfR, transferrin receptor

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