Regulation of transferrin receptor expression in term human cytotrophoblasts

Abstract

Placental transferrin receptors (TfR's) located at the apical side of syncytiotrophoblast, mediate placental iron uptake. Changes in TfR density on the maternal-fetal exchange area will immediately affect placental iron uptake. Therefore, this could be a major determinant in the regulation of maternal-fetal iron transport. We have studied mechanisms that might influence TfR expression in cultured human term cytotrophoblasts. These cells are notproliferative in vitro. In many proliferating cell types growth factors, like insulin, cause a redistribution of TfR's from cytosolic pools to the cell surface. Our experiments show that addition of insulin to, or withdrawal of serum from the culture medium does not lead to a change in cell surface TfR levels in term cytotrophoblasts, thus suggesting that the redistribution effect in linked to the mitogenic role of growth factors. Addition of extra iron to the culture medium leads to down-regulation of trophoblast TfR levels. This suggests that Iron-Responsive-Elements, operative in many cell types except in macrophages are involved in the regulation of placental iron uptake. Thus, transplacental iron transport can be protected against iron overload and iron deficiency.