Iron deficiency anemia is the most common nutritional disorder in the world. Anemia is especially serious during pregnancy,
with deleterious consequences for both the mother and her developing fetus. ...We have developed a model to investigate the mechanisms
whereby fetal growth and development are affected by maternal anemia. Weanling rats were fed a control or iron-deficient diet
before and throughout pregnancy and were killed at Day 21. Dams on the deficient diet had lower hematocrits, serum iron concentrations,
and liver iron levels. Similar results were recorded in the fetus, except that the degree of deficiency was markedly less,
indicating compensation by the placenta. No effect was observed on maternal weight or the number and viability of fetuses.
The fetuses from iron-deficient dams, however, were smaller than controls, with higher placental:fetal ratios and relatively
smaller livers. Iron deficiency increased levels of tumor necrosis factor α (TNFα) only in the trophoblast giant cells of
the placenta. In contrast, levels of type 1 TNFα receptor increased significantly in giant cells, labyrinth, cytotrophoblast,
and fetal vessels. Leptin levels increased significantly in labyrinth and marginally ( P = 0.054) in trophoblast giant cells. No change was observed in leptin receptor levels in any region of the placentas from
iron-deficient dams. The data show that iron deficiency not only has direct effects on iron levels and metabolism but also
on other regulators of growth and development, such as placental cytokines, and that these changes may, in part at least,
explain the deleterious consequences of maternal iron deficiency during pregnancy.
Maternal iron deficiency during pregnancy induces anaemia in the developing fetus; however, the severity tends to be less than in the mother. The mechanism underlying this resistance has not been ...determined. We have measured placental expression of proteins involved in iron transfer in pregnant rats given diets with decreasing levels of iron and examined the effect of iron deficiency on iron transfer across BeWo cell layers, a model for placental iron transfer. Transferrin receptor expression was increased at both mRNA and protein levels. Similarly, expression of the iron-responsive element (IRE)-regulated form of the divalent metal transporter 1 (DMT1) was also increased. In contrast, the non-IRE regulated isoform showed no change in mRNA levels. Protein levels of DMT1 increased significantly. Iron efflux is thought to be mediated by the metal transporter protein, IREG1/ferroportin1/MTP1, and oxidation of Fe(II) to Fe(III) prior to incorporation into fetal transferrin is carried out by the placental copper oxidase. Expression of IREG1 was not altered by iron deficiency, whereas copper oxidase activity was increased. In BeWo cells made iron deficient by treatment with desferrioxamine ('deferioxamine'), iron accumulation from iron-transferrin increased, in parallel with increased expression of the transferrin receptor. At the same time, iron efflux also increased, showing a higher flux of iron from the apical to the basolateral side. The data show that expression of placental proteins of iron transport are up-regulated in maternal iron deficiency, resulting in an increased efficiency of iron flux and a consequent minimization of the severity of fetal anaemia.
Maternal iron deficiency during pregnancy induces anaemia in the developing fetus; however, the severity tends to be less than in the mother. The mechanism underlying this resistance has not been ...determined. We have measured placental expression of proteins involved in iron transfer in pregnant rats given diets with decreasing levels of iron and examined the effect of iron deficiency on iron transfer across BeWo cell layers, a model for placental iron transfer. Transferrin receptor expression was increased at both mRNA and protein levels. Similarly, expression of the iron-responsive element (IRE)-regulated form of the divalent metal transporter 1 (DMT1) was also increased. In contrast, the non-IRE regulated isoform showed no change in mRNA levels. Protein levels of DMT1 increased significantly. Iron efflux is thought to be mediated by the metal transporter protein, IREG1/ferroportin1/MTP1, and oxidation of Fe(II) to Fe(III) prior to incorporation into fetal transferrin is carried out by the placental copper oxidase. Expression of IREG1 was not altered by iron deficiency, whereas copper oxidase activity was increased. In BeWo cells made iron deficient by treatment with desferrioxamine (‘deferioxamine’), iron accumulation from iron-transferrin increased, in parallel with increased expression of the transferrin receptor. At the same time, iron efflux also increased, showing a higher flux of iron from the apical to the basolateral side. The data show that expression of placental proteins of iron transport are up-regulated in maternal iron deficiency, resulting in an increased efficiency of iron flux and a consequent minimization of the severity of fetal anaemia.
Iron deficiency anemia is the most common nutritional disorder in the world. Anemia is especially serious during pregnancy, with deleterious consequences for both the mother and her developing fetus. ...We have developed a model to investigate the mechanisms whereby fetal growth and development are affected by maternal anemia. Weanling rats were fed a control or iron-deficient diet before and throughout pregnancy and were killed at Day 21. Dams on the deficient diet had lower hematocrits, serum iron concentrations, and liver iron levels. Similar results were recorded in the fetus, except that the degree of deficiency was markedly less, indicating compensation by the placenta. No effect was observed on maternal weight or the number and viability of fetuses. The fetuses from iron-deficient dams, however, were smaller than controls, with higher placental:fetal ratios and relatively smaller livers. Iron deficiency increased levels of tumor necrosis factor α (TNFα) only in the trophoblast giant cells of the placenta. In contrast, levels of type 1 TNFα receptor increased significantly in giant cells, labyrinth, cytotrophoblast, and fetal vessels. Leptin levels increased significantly in labyrinth and marginally (P = 0.054) in trophoblast giant cells. No change was observed in leptin receptor levels in any region of the placentas from iron-deficient dams. The data show that iron deficiency not only has direct effects on iron levels and metabolism but also on other regulators of growth and development, such as placental cytokines, and that these changes may, in part at least, explain the deleterious consequences of maternal iron deficiency during pregnancy.
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