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.
Rowett Research Institute, Aberdeen, UK.
Lorraine
L
Gambling
Ruth
R
Danzeisen
Cedric
C
Fosset
Henriette S
HS
Andersen
Susan
S
Dunford
S Kaila S
SK
Srai
Harry J
HJ
MCArdle
D000818:Animals; D003300:Copper / Q000378:metabolism*; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011256:Pregnancy Outcome
D003300:Copper; D007501:Iron