Iron deficiency in the pregnant rat has differential effects on maternal and fetal copper levels.

Iron deficiency during pregnancy causes problems both for the mother and fetus. Iron deficiency is known to have secondary effects on copper metabolism. In this study, we use a rat model to examine the effect of iron deficiency on copper levels in maternal and fetal tissue. We assess whether the effects of iron deficiency on copper metabolism are due to alterations in mRNA levels of proteins of copper transport. Rowett Hooded Lister rats were fed diets with four different iron contents before and during pregnancy. Maternal and fetal samples were collected on day 21 of gestation. Copper and iron levels of liver and placenta were analyzed, mRNA levels of genes involved in copper transport were studied, and copper oxidase activity measured. Reduced dietary iron was found to increase maternal liver copper, inversely correlating with iron levels. Correspondingly, copper and ceruloplasmin increased in maternal serum. The placenta showed the greatest increase in copper levels. As the iron content of the maternal diet decreased so did the iron and copper levels in the fetal liver. In all tissues examined, mRNA expression for CTR1, ATOX1, ATP7A, and ATP7B was unchanged by iron deficiency. However, copper oxidase activity in maternal serum and placenta was increased. Our study in a rat model demonstrates that iron deficiency during pregnancy has a differential effect on copper metabolism in the mother and fetus. It is clear from this study that the changes in copper levels that accompany iron deficiency are not mediated by changes in transcription of the genes involved in copper transport.

Estrogen and progesterone regulate alpha, beta, and gammaENaC subunit mRNA levels in female rat kidney.

BACKGROUND: Estrogen and progesterone regulate alpha, beta, and gamma amiloride-sensitive epithelial sodium channel (ENaC) subunit mRNA levels in female rat kidney. Renal Na(+) handling differs between males and females. Further, within females Na(+) metabolism changes during the menstrual cycle and pregnancy. Electrolyte homeostasis and extracellular fluid volume are maintained primarily by regulated transport of Na(+) via the amiloride-sensitive Na(+) channel. This study examines the role of the female gender steroids in the regulation of expression of ENaC. METHODS: We measured ENaC subunit mRNA levels in rat kidney using Northern blotting. Kidneys were taken from male and females at different ages and from adult ovariectomized rats treated with 17-beta-estradiol benzoate (estrogen) and/or progesterone for 8 or 24 hours. RESULTS: The abundance of alpha, beta, and gammaENaC mRNA was significantly higher in female compared to male rat kidneys from 10 weeks of age (P= 0.001, P= 0.004, and P= 0.02, N= 10, respectively). These differences were abolished in ovariectomized rats. Treatment of ovariectomized rats with estrogen increased alphaENaC mRNA abundance in the kidney at both 8 and 24 hours (P < 0.05, N= 6; and P < 0.05, N= 7, respectively). Progesterone inhibited the effect of estrogen on alphaENaC mRNA at 8 hours but when given alone increased gammaENaC mRNA (P < 0.05, N= 3). Neither hormone, alone or in combination, had any significant effect on betaENaC mRNA levels at 8 or 24 hours. CONCLUSION: Female gonadal steroids differentially modulate expression of ENaC subunit mRNA in the rat kidney.

Iron deficiency during pregnancy affects postnatal blood pressure in the rat.

Iron (Fe) deficiency anaemia during pregnancy results in an increased risk of perinatal mortality and morbidity and is a significant factor for increased risk of disease in later life. Consequently we have developed a rat model to study the relationship between maternal Fe deficiency and postnatal growth and blood pressure in the offspring. Weanlings were fed a control or Fe-deficient diet prior to and throughout pregnancy. At term, all pups were cross-fostered to control fed dams and weaned onto control diet. At birth, pups from deficient dams had a greater mortality rate, were smaller and had reduced haematocrit and liver Fe levels. They also had larger hearts, smaller kidneys and spleens and unchanged livers (relative organ weight). The pups grew normally. At 6 weeks, male pups from deficient dams had a higher and females a lower blood pressure than their normal counterparts. At 10 and 16 weeks, blood pressure in the males from deficient dams was still raised and in the females was now greater than controls. The haematocrit was lower in males throughout the 16 weeks and in females until 10 weeks of age. There was no significant difference in the offsprings' liver Fe stores at 6, 10 or 16 weeks. Duodenal Fe uptake in both the Fe-deficient mother and newborn offspring was significantly increased. By cross-fostering, we have eliminated confounding factors, such as maternal anaemia during lactation and show, unequivocally, that prenatal nutrition is critical for the development of normal postnatal function.

Iron and copper interactions in development and the effect on pregnancy outcome.

During pregnancy, nutrients are transferred from mother to fetus across the placenta. The mechanisms whereby this occurs, and the adaptations that occur in response to deficiency or overload of iron (Fe) and copper (Cu) are examined in this review. Fe deficiency during pregnancy is common and has serious consequences both in the short and the long term such as fetal growth retardation and cardiovascular problems in the adult offspring. Similarly, Cu deficiency, although not so common, also has deleterious effects. The placenta minimizes the effect of the deficiency by up-regulating the proteins involved in Fe transfer. For example, transferrin receptor levels increase inversely to maternal Fe levels. Divalent metal transporter 1 (DMT1) mRNA in the iron-responsive element (IRE) regulated, but not the non-IRE regulated form is increased, as is the placenta Cu oxidase. Conversely, iron-regulated gene 1 (IREG1) expression is not affected. Fe deficiency increases Cu levels in maternal liver, serum and placenta, but has much less effect in the fetal serum and liver. Apart from maternal ceruloplasmin, mRNA levels of Cu-related proteins are not changed. The Cu oxidase, which we suggest fulfils the function of hephaestin in placenta, is regulated by Cu as well as by Fe. Fe deficiency also has marked effects on cytokine levels in the placenta. Tumor necrosis factor alpha (TNFalpha) and TNFalpha receptor 1 (TNFalphaR1) levels both increase. The data show that altering Fe status has a marked effect on metabolism of other metals and of other important mediators of cell function. This is particularly important during pregnancy, when the developing fetus is very vulnerable to inappropriate micronutrient status.