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. 2016 May 30;74(7):421–431. doi: 10.1093/nutrit/nuw009

Table 1.

Function and localization of iron transporter proteins in human and mouse placentaea

Proposed function Protein Localization in human placenta Localization in mouse placenta
Apical iron uptake
Transferrin
  • Syncytiotrophoblast: strong, continuous staining on apical membrane23

  • Other locations: fetal stroma23

No localization data
TFR1
  • Syncytiotrophoblast: strong, continuous staining on apical membrane23,47,48

  • Other locations: cytotrophoblasts, fetal stromal macrophages, fetal endothelium48

Strong, predominant staining on apical membrane of labyrinth trophoblasts; also stains fetal endothelium at E1020
HFE
  • Syncytiotrophoblast: staining confined to basal23 or apical membrane49

  • Other locations: fetal stromal macrophages23

No localization data
SCARA5
  • Syncytiotrophoblast: weak cytoplasmic and membranous staining50

  • Other locations: fetal endothelium50

No localization data
ZIP8
  • Syncytiotrophoblast: strong, continuous staining on apical membrane; weak cytoplasmic staining50

  • Other locations: fetal endothelium50

No localization data
Intracellular iron trafficking
ZIP14 Syncytiotrophoblast: strong cytoplasmic and membranous staining50 No localization data
DMT1
  • Syncytiotrophoblastb: punctuate and diffused staining in cytoplasm and basal membrane23,47; continuous staining in cytoplasm and apical membrane45,46

  • Other locations: fetal stroma,23,51 fetal stromal macrophages47

No localization data
Ferritin
  • Syncytiotrophoblast: very weak/negative staining23,50,51; predominant staining toward apical side52

  • Other locations: fetal stroma,23,52 fetal endothelium51

No localization data
STEAP3 Syncytiotrophoblast: weak and diffuse cytoplasmic staining; intense and granular staining along basal membrane50 No localization data
STEAP4 No localization data No localization data
Basolateral iron export
FPN1
  • Syncytiotrophoblast: strong, continuous staining on basal side23,53

  • Other locations: fetal stromal macrophages23

Strong, continuous staining in labyrinth trophoblasts at E16.554
Ceruloplasmin
  • Syncytiotrophoblastb: intense55 or weak diffuse staining56

  • Other locations: fetal stroma,55 intervillous space, fetal endothelium56

No localization data
Hephaestin Syncytiotrophoblast: membranous and cytoplasmic staining 50 No localization data
Zyklopen No localization data Labyrinth trophoblasts and spongiotrophoblasts at E15.557
Heme iron metabolism
HRG1 No localization data No localization data
LRP1
  • Syncytiotrophoblast: strong cytoplasmic staining, more intense on apical side58

  • Other locations: fetal stromal macrophages58

Strong staining in ectoplacental cone at E7.559
PCFT
  • Syncytiotrophoblast: cytoplasmic and membranous staining, more intense on apical side60

  • Other locations: fetal endothelium60

Weak staining in labyrinth trophoblasts, spongiotrophoblasts, trophoblast giant cells, and fetal endothelium at E12.5–18.561
FLVCR1
  • Syncytiotrophoblast: cytoplasmic and membranous staining, more intense on apical side50

  • Other locations: fetal stromal macrophages

  • No protein localization data

  • High mRNA expression in labyrinth trophoblasts, spongiotrophoblasts, and trophoblast giant cells from E9.5 to term62

FLVCR2
  • Syncytiotrophoblast: cytoplasmic and membranous staining, very intense on apical side50

  • Other locations: cytotrophoblasts50

No localization data
HO1
  • Syncytiotrophoblastb: intense63,64 or negative/very weak staining65,66

  • Other locations: fetal endothelium,63,64 cytotrophoblasts63

Labyrinth trophoblasts2: positive staining at E1367; negative staining at E14.568; strong staining in spongiotrophoblasts at E13 and E14.567,68
HO2
  • Syncytiotrophoblastb: strong,63 weak,65,66 or negative staining64

  • Other locations: fetal endothelium63–66

Moderate staining in labyrinth trophoblasts, spongiotrophoblasts, and trophoblast giant cells at E13; weak staining in fetal endothelium67

aAll human data are from studies in term healthy placentae; mouse studies represent expression after the formation of mature placenta at E10.5, if data are available. Subcellular locations of some proteins are not described because the immunohistochemistry images are at low resolution.

bDenotes inconsistent findings.

Abbreviations: DMT1, divalent metal transporter 1; E, embryonic day; FLVCR, feline leukemia virus subgroup C cellular receptor; FPN, ferroportin; HO, heme oxygenase; HRG, heme-responsive gene; LRP, low-density lipoprotein receptor-related protein; PCFT, protein-coupled folate transporter; SCARA5, scavenger receptor class A member 5; STEAP, six-transmembrane epithelial antigen of the prostate; TF, transferrin; TFR1, transferrin receptor 1; ZIP, Zrt- and Irt-like protein.