Table 1.
Function and localization of iron transporters in placenta.
| Protein (Gene) | Function | Localization in Human Placenta | Disruption and Phenotype |
|---|---|---|---|
| TfR1 (TFRC) | TBI and ferritin uptake | On the apical membrane of STB [39] |
Trfc−/− was embryonic lethal at E12.5; Trfc+/− mice showed severe anemia [43] |
| DMT1 (DMT1; SLC11A2) | Intracellular iron trafficking | Prominently near maternal side; rarely on fetal side; scatter staining in stroma [44] |
Slc11a2−/− mice were pale at birth; not iron deficient in all tissues comparing to wildtype littermates; Slc11a2+/− mice were viable without visible abnormalities [45] |
| ZIP14 (SLC39A14) | NTBI uptake and intracellular iron trafficking | Not available | SLC39A14−/− mice were viable with growth retardation; iron relating parameters not reported [46] |
| ZIP8 (SLC39A8) | NTBI uptake and intracellular iron trafficking | Not available | SLC39A8neo/neo newborns were pale and growth was stunted with diminished iron uptake [47] |
| Hephaestin (HEPH) | Ferroxidases | Not available | Mice with global or intestine-specific knockout of Heph were viable with microcytic anemia due to reduced intestinal iron absorption [48,49] |
| Ceruloplasmin (CP) | Ferroxidases | Intervillous space [50] | Although normal at birth, Cp−/− mice showed progressive accumulation of iron in liver and spleen, but not in macrophages [51,52] |
| Zyklopen (ZP, HEPHL1) | Ferroxidases | Cytoplasm of STB [53]; maternal decidua [54] | Zp−/− showed increased placenta size with no change in fetal iron transfer [54] |
| SCARA5 (SCARA5) | Ferritin uptake | Not available | Not available |
| FLVCR1 (FLVCR1) | Heme uptake | Not available | FLVCR1−/− was embryonic lethal at E7.5 due to impaired erythropoiesis [55] |
| BCRP (ABCG2) | Heme uptake | On the apical membrane of STB [56] | ABCG2−/− mice were viable; iron relating parameters not reported [57] |
| LRP1 (LRP1) | Heme uptake | Not available | LRP1−/− was embryonic lethal at E12.5 [58] |
| HO-1 (HO1) | Heme iron metabolism | In STB and cytotrophoblasts [59] | HO1−/− decreased embryo viability; HO1+/− led to placental dysfunction; iron relating parameters not reported [60] |
| FPN (FPN, SLC40A1) | Iron export | On the basolateral membrane of STB | SLC40A1−/− causes embryo lethality before E7.5; Meox2-Cre; Fpnflox/flox mice, in which FPN was only expressed in placenta, were viable with anemia and cellular iron accumulation [10] |
Abbreviations: TfR1, transferrin receptor 1; TBI, transferrin-bound iron; STB, syncytiotrophoblasts; E, embryonic day; DMT1, divalent metal transporter 1; ZIP, Zrt/Irt-like protein; NTBI, non-transferrin-bound iron; SCARA5, scavenger receptor class A member 5; FLVCR1, feline leukemia virus subgroup C receptor 1; BCRP, breast cancer resistance protein; LRP1, LDL-receptor-related protein 1; HO, heme oxygenase; FPN, ferroportin.