Identification and localization of divalent metal transporter-1 (DMT-1) in term human placenta

The mechanism by which iron is transported from mother to fetus is incompletely understood. Whereas transferrin receptor (TfR) is responsible for iron uptake from maternal serum by the syncytiotrophoblast, the proteins responsible for intracytoplasmic transport and for delivery to the fetal serum remain unknown. The aim of this study was to determine whether the recently characterized endosomal membrane iron transporter, divalent metal ion transporter-1 (DMT-1), is expressed in human syncytiotrophoblast, and whether its cellular localization would support roles for cytoplasmic and placental-fetal iron transport. Six micron sections of frozen, term human placenta were assessed immunohistochemically using a polyclonal antibody to rat DMT-1 and a monoclonal antibody to human TfR. DMT-1 was found both in the cytoplasm and at the junction of the fetal (basal) membrane and fetal vessels, while TfR was localized predominantly to the maternal (apical) side of the syncytiotrophoblastic membrane. Double staining demonstrated no overlap between the two proteins on the apical membrane and minimal areas of overlap in the cytoplasm. We postulate that the syncytiotrophoblast takes up diferric transferrin from serum via TfR, subsequently incorporating the transferrin : TfR complex via endosomes. Subsequent transport of iron out of the endosome and across the basal membrane to the fetus may occur via DMT-1.