Maternal Zinc Deprivation and Interleukin-1 Influence Metallothionein Gene Expression and Zinc Metabolism of Rats

Abstract

The influence of maternal dietary zinc intake and recombinant human interleukin-1 alpha (rhIL-1 alpha) administration on metallothionein gene expression and the distribution of 65Zn were investigated. Pregnant rats were fed diets containing 1, 5, 30 or 180 mg Zn/kg diet in an equalized regime from d 13-20 of gestation. Metallothionein gene expression was examined by Northern blot and dot blot hybridization using combined 60-mer oligonucleotides specific for rat metallothionein-1 and -2 genes. Expression was progressively depressed in the fetal livers and livers and kidneys of dams fed diets marginal (5 mg/kg) and deficient (1 mg/kg) in zinc content. Administration of rhIL-1 alpha increased expression in maternal liver, placenta and in fetal liver of dams fed adequate or deficient diets. Kinetics of intravenously administered 65Zn showed that in response to rhIL-1 alpha, there was a higher uptake by the maternal liver and bone marrow with less 65Zn uptake by bone, intestine and plasma activity compared to controls. No change was observed in 65Zn taken up by the placenta or transferred to the fetus. Alteration of metallothionein gene expression could represent, in part, the mechanism whereby altered effects of zinc metabolism and function are mediated during fetal development.