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

The mechanism by which iron is transported from mother to fetus is incomple tely understood. Whereas transferrin receptor (TfR) is responsible for iron uptake from maternal serum by the syncytiotrophoblast, the proteins respon sible for intracytoplasmic transport and for delivery to the fetal serum re main unknown. The aim of this study was to determine whether the recently c haracterized endosomal membrane iron transporter, divalent metal ion transp orter-1 (DMT-1), is expressed in human syncytiotrophoblast, and whether its cellular localization would support roles for cytoplasmic and placental-fe tal iron transport. Six micron sections of frozen, term human placenta were assessed immunohistochemically using a polyclonal antibody to rat DMT-1 an d 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 syncy tiotrophoblastic 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 tra nsferrin from serum via TfR, subsequently incorporating the transferrin : T fR complex via endosomes. Subsequent transport of iron out of the endosome and across the basal membrane to the fetus may occur via DMT-1. (C) 2000 Ha rcourt Publishers Ltd.