title: Fetal iron levels are regulated by maternal and fetal Hfe genotype and dietary iron.
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.
  
  
  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.
authors.affiliation: Department of Structural and Molecular Biology, Division of Biosciences, University College London, London, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Balesaria
authors.forename: Rumeza
authors.initials: R
authors.lastname: Hanif
authors.forename: Mohamed F
authors.initials: MF
authors.lastname: Salama
authors.forename: Kishor
authors.initials: K
authors.lastname: Raja
authors.forename: Henry K
authors.initials: HK
authors.lastname: Bayele
authors.forename: Harry
authors.initials: H
authors.lastname: McArdle
authors.forename: Surjit K S
authors.initials: SK
authors.lastname: Srai
mesh_terms: D000824:Animal Nutritional Physiological Phenomena / Q000235:genetics*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D015153:Blotting, Western; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005333:Fetus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D007501:Iron / Q000378:metabolism*; D019266:Iron, Dietary / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D008297:Male; D008431:Maternal-Fetal Exchange; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D023181:Antimicrobial Cationic Peptides; C579599:Hamp protein, mouse; D000071020:Hemochromatosis Protein; D064451:Hepcidins; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D019266:Iron, Dietary; D008565:Membrane Proteins; D012333:RNA, Messenger; D007501:Iron