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

Abstract

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

Umbilical cord trace elements and minerals and risk of early childhood wheezing and eczema

“…The Avon Longitudinal Study of Parents and Children (ALSPAC) [16,17] is a prospective study of 14,541 pregnancies that resulted in 14,062 live births, of whom 13,971 survived to 1 yr. Females were enrolled as early in pregnancy as possible, on the basis of an expected date of delivery between April 1, 1991 and December 31, 1992, and place of residence within the three Bristol-based health districts of the former county of Avon, UK.…”

“…Therefore, the current authors postulated that a high foetal exposure to the antioxidant trace elements (selenium, zinc, copper and manganese) might decrease the risk of wheezing and eczema in early childhood, and that high foetal exposure to lead and mercury might increase the risk of these conditions. The present authors speculated that a low foetal exposure to iron might play a role in aetiology, as this causes impaired foetal growth in animals [14], and that a low foetal exposure to magnesium might be a risk factor for wheezing, in view of an association later in life between dietary intake and bronchial hyperresponsiveness (BHR) [15].…”

“…In animals there is some evidence that maternal selenium deficiency during pregnancy leads to impaired lung development in the offspring [8]. Whilst maternal iron deficiency causes foetal growth retardation [14], effects on foetal lung growth do not appear to have been studied.…”

“…Effects of iron deficiency in pregnancy on placental production of cytokines have been reported in animals [14], although whether maternal iron status would have any influence on Th1/Th2 responses, given that the immunological milieu at the foeto-maternal interface is normally Th2-skewed [33], is unclear. There is some evidence to suggest that iron deficiency or iron reduction therapy later in life may upregulate Th2 cytokine responses and downregulate Th1 responses [34,36].…”

Plasma concentrations and placental immunostaining of interleukin-10 and tumornecrosis factor-α as predictors of alterations in the embryo-fetal organism and the placental development of diabetic rats

“…The intensity of immunolocalization in each placental zone was analyzed by two independent readers and averaged. Signal intensity was scored as follows: 1, not detectable; 2, weak; 3, moderate; 4, high (8).…”