In vivo evidence for the functional heterogeneity of transferrin-bound iron. II. Studies in pregnant rats.

Iron atoms from the two iron-binding sites of transferrin in the maternal plasma were selectively transferred to fetal tissues across the placenta of the pregnant rat. Rat serum transferrin was selectively double-labeled with 55Fe bound to the A-site and 59Fe bound to the B-site and injected intravenously into pregnant rats at 11 to 20 days gestation. Ratios of 55Fe to 59Fe were measured in various maternal and fetal tissues sampled from 30 to 120 minutes after injection. In the maternal tissues preponderance of A-site 55Fe was observed in circulating red blood cells and in heme extracted from bone marrow and spleen; B-site 59Fe predominated in the liver parenchymal cells and proximal small intestine. As predicted by the Fletcher-Huehns hypothesis, placental transfer of radioiron resulted in a selective concentration of A-site 55Fe in all the fetal tissues including the fetal placenta, yolk sac, whole fetus, and in the separately analyzed liver heme and ferritin and in fetal blood. When the placenta was bypassed by direct injection of the selectively double-labeled transferrin into the umbilical vein, a reversal of the 55Fe/59Fe ratios of heme extracted from the fetal liver was observed. These studies confirm the concept of functional heterogeneity of iron atoms bound to transferrin and indicate that the placenta of rats between the eleventh and twentieth day of pregnancy selectively removes erythroblast-oriented iron from transferrin and diverts it to fetal tissues.