The placental syncytiotrophoblast is involved in iron transfer from mother to fetus during pregnancy.
The fetus completely depends on maternal iron supply and the placenta can adapt to iron deficiency or overload by regulating the proteins that are thought to be involved in iron transport and storage.
Diferric transferrin – mainly synthesized by maternal hepatocytes but also produced by villous mononucleated cytotrophoblasts (CTB) and syncytiotrophoblast (STB) – is the most important iron source.
It is thought that transferrin uptake, iron release and recycling of apotransferrin in STB occur as in all other human cells (Iron input). This involves clathrin-mediated internalization of the transferrin – TfnR complex, iron release in acidic early endosomes at pH 6.0, recycling of apotransferrin via perinuclear recycling compartments (pH 6.4) and subsequent release of apotransferrin into the (maternal) circulation. (Transferrin cycle)
In the endosome, ferric iron (Fe3) is thought to be reduced by a ferrireductase to ferrous iron (Fe2), which then becomes a substrate for the divalent metal transporter DMT1/Nramp2 for transfer into the cytoplasm, where it can be stored (bound to ferritin or as labile iron pool), used for biosynthesis or, as in villous enterocytes, transported across the basolateral membrane by another putative cation transporter, ferroportin/IREG1/MTP1/SLC40. Iron release at the basolateral side of villus enterocytes and iron loading to apotransferrin can be facilitated by the ferroxidase activity of (plasma) ceruloplasmin or hephaestin due to oxidation to Fe3 [R Fuchs et al, 2004].