Contrasting effects of a dietary copper deficiency in male and female mice

Female rats are protected from the lethal effects of a dietary copper (Cu) deficiency, but female mice fed a Cu-deficient diet develop atrial thromboses and die. To further investigate the effect of sex on Cu status in mice (n = 16), male and female adult Swiss-Webster mice were fed Cu-supplemented (8.4 mg Cu/kg) or Cu-deficient (0.3 mg Cu/kg) diets with deionized water for 43-49 days. Six female mice, but only one male mouse, fed the Cu-deficient diet died during the experiment. Both male and female mice fed the Cu-deficient diet exhibited typical features of deficiency. The severity of anemia and the values observed for several indicators of Cu status (plasma ceruloplasmin [EC 1.16.3.1.] and erythrocyte copper-zinc superoxide dismutase [EC 1.15.1.1.] activities, cardiac Cu) were similar in both male and female Cu-deficient mice. However, cardiac enlargement (0.97 vs 0.73 g/100 g body wt, P < 0.05), cardiac edema (79.9% vs 78.2% cardiac water, P < 0.05) and depletion of renal Cu (10.4 vs 12.5 micrograms/g dry weight, P < 0.05) were more severe in female compared with male, Cu-deficient mice. Furthermore, although hepatic Cu was significantly (P < 0.05) lower in female Cu-deficient compared with Cu-supplemented mice, it was not significantly decreased by deficiency in male mice. These data indicate that the female mice experienced a more extreme form of Cu deficiency than the males.