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Effect of Iron Deficiency on Placental Cytokine Expression and Fetal Growth in the Pregnant Rat¹

^a The Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB, United Kingdom

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 (TNF) only in the trophoblast giant cells of the placenta. In contrast, levels of type 1 TNF 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.

First decision: 10 July 2001.

¹ Supported by the Scottish Executive Rural Affairs Department, the European Union (QLK1-1999-00337), the Rank Prize Funds, and COST D8.

² Correspondence: Harry J. McArdle, The Rowett Research Institute, Greenburn Rd., Bucksburn, Aberdeen AB21 9SB, U.K. FAX: 01224 716622; hjm{at}rri.sari.ac.uk

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