Fetal iron levels are regulated by maternal and fetal Hfe genotype and dietary iron

Sara Balesaria, Rumeza Hanif, Mohamed F Salama, Kishor Raja, Henry K Bayele, Harry J McArdle, Surjit K S Srai

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background Iron metabolism during pregnancy maintains fetal iron levels at the expense of the mother. The mechanism behind this regulation is still not clear despite recent advances. Here we examine the role of maternal and fetal Hfe, its downstream signaling molecule, hepcidin and dietary iron in the regulation of placental iron transfer.

Design and Methods Hfe wild-type, knockout and heterozygote dams were fed iron deficient (12.5 ppm), adequate (50 ppm) and replete (150 ppm) iron diets and mated with heterozygote males to produce pups of all genotypes. Dams and pups were sacrificed at Day 18 of gestation; serum, placenta, body and liver iron parameters were measured. Protein and mRNA levels of various iron transporter genes were determined in duodenum, liver and placenta by Western blotting and real time PCR.

Results Maternal liver iron levels were dependent on both dietary iron intake and Hfe genotype. Increasing iron levels in the maternal diet resulted in increased total iron in the fetus, primarily in the liver. However, fetuses of Hfe-knockout mothers showed further elevation of liver iron levels, concomitant with elevated expression of Tfr1, Dmt1 and Fpn in the placenta. Hfe-knockout fetuses that express low levels of liver hepcidin accumulated more iron in their liver than wild-type fetuses due to increased ferroportin levels in the placenta.

Conclusions Maternal and fetal status, as well as dietary iron, is important in regulating iron transfer across placenta. Maternal Hfe regulates iron transfer by altering gene expression in the placenta. Fetal Hfe is important in regulating placental iron transfer by modulating fetal liver hepcidin expression.

Original languageEnglish
Pages (from-to)661-669
Number of pages9
JournalHaematologica
Volume97
Issue number5
Early online date16 Dec 2011
DOIs
Publication statusPublished - 1 May 2012

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Dietary Iron
Iron
Genotype
Mothers
Placenta
Liver
Hepcidins
Fetus
Heterozygote
Diet
Pregnancy

Keywords

  • iron
  • fetal Hfe
  • dietary
  • genotype
  • maternal

Cite this

Balesaria, S., Hanif, R., Salama, M. F., Raja, K., Bayele, H. K., McArdle, H. J., & Srai, S. K. S. (2012). Fetal iron levels are regulated by maternal and fetal Hfe genotype and dietary iron. Haematologica, 97(5), 661-669. https://doi.org/10.3324/haematol.2011.055046

Fetal iron levels are regulated by maternal and fetal Hfe genotype and dietary iron. / Balesaria, Sara; Hanif, Rumeza; Salama, Mohamed F; Raja, Kishor; Bayele, Henry K; McArdle, Harry J; Srai, Surjit K S.

In: Haematologica, Vol. 97, No. 5, 01.05.2012, p. 661-669.

Research output: Contribution to journalArticle

Balesaria, S, Hanif, R, Salama, MF, Raja, K, Bayele, HK, McArdle, HJ & Srai, SKS 2012, 'Fetal iron levels are regulated by maternal and fetal Hfe genotype and dietary iron', Haematologica, vol. 97, no. 5, pp. 661-669. https://doi.org/10.3324/haematol.2011.055046
Balesaria, Sara ; Hanif, Rumeza ; Salama, Mohamed F ; Raja, Kishor ; Bayele, Henry K ; McArdle, Harry J ; Srai, Surjit K S. / Fetal iron levels are regulated by maternal and fetal Hfe genotype and dietary iron. In: Haematologica. 2012 ; Vol. 97, No. 5. pp. 661-669.
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AU - Bayele, Henry K

AU - McArdle, Harry J

AU - Srai, Surjit K S

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N2 - Background Iron metabolism during pregnancy maintains fetal iron levels at the expense of the mother. The mechanism behind this regulation is still not clear despite recent advances. Here we examine the role of maternal and fetal Hfe, its downstream signaling molecule, hepcidin and dietary iron in the regulation of placental iron transfer. Design and Methods Hfe wild-type, knockout and heterozygote dams were fed iron deficient (12.5 ppm), adequate (50 ppm) and replete (150 ppm) iron diets and mated with heterozygote males to produce pups of all genotypes. Dams and pups were sacrificed at Day 18 of gestation; serum, placenta, body and liver iron parameters were measured. Protein and mRNA levels of various iron transporter genes were determined in duodenum, liver and placenta by Western blotting and real time PCR. Results Maternal liver iron levels were dependent on both dietary iron intake and Hfe genotype. Increasing iron levels in the maternal diet resulted in increased total iron in the fetus, primarily in the liver. However, fetuses of Hfe-knockout mothers showed further elevation of liver iron levels, concomitant with elevated expression of Tfr1, Dmt1 and Fpn in the placenta. Hfe-knockout fetuses that express low levels of liver hepcidin accumulated more iron in their liver than wild-type fetuses due to increased ferroportin levels in the placenta. Conclusions Maternal and fetal status, as well as dietary iron, is important in regulating iron transfer across placenta. Maternal Hfe regulates iron transfer by altering gene expression in the placenta. Fetal Hfe is important in regulating placental iron transfer by modulating fetal liver hepcidin expression.

AB - Background Iron metabolism during pregnancy maintains fetal iron levels at the expense of the mother. The mechanism behind this regulation is still not clear despite recent advances. Here we examine the role of maternal and fetal Hfe, its downstream signaling molecule, hepcidin and dietary iron in the regulation of placental iron transfer. Design and Methods Hfe wild-type, knockout and heterozygote dams were fed iron deficient (12.5 ppm), adequate (50 ppm) and replete (150 ppm) iron diets and mated with heterozygote males to produce pups of all genotypes. Dams and pups were sacrificed at Day 18 of gestation; serum, placenta, body and liver iron parameters were measured. Protein and mRNA levels of various iron transporter genes were determined in duodenum, liver and placenta by Western blotting and real time PCR. Results Maternal liver iron levels were dependent on both dietary iron intake and Hfe genotype. Increasing iron levels in the maternal diet resulted in increased total iron in the fetus, primarily in the liver. However, fetuses of Hfe-knockout mothers showed further elevation of liver iron levels, concomitant with elevated expression of Tfr1, Dmt1 and Fpn in the placenta. Hfe-knockout fetuses that express low levels of liver hepcidin accumulated more iron in their liver than wild-type fetuses due to increased ferroportin levels in the placenta. Conclusions Maternal and fetal status, as well as dietary iron, is important in regulating iron transfer across placenta. Maternal Hfe regulates iron transfer by altering gene expression in the placenta. Fetal Hfe is important in regulating placental iron transfer by modulating fetal liver hepcidin expression.

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