The timing of perinatal copper deficiency in mice influences offspring survival

Copper is an essential metal during development. Female Swiss Webster mice were fed a modified AIN-76A diet low in copper (0.3 mg Cu/kg and 43 mg Fe/kg; -Cu). One-half the mice received copper in their drinking water (20 mg Cu/L; +Cu). Female mice were mated to normal males and offered the -Cu or +Cu treatments starting at gestational d 13. Treatments did not affect litter size or pregnancy outcome. For three litters of +Cu mice, 26/26 offspring born were weaned on postnatal d 21 (P21). For three litters of -Cu dams, 0/26 pups survived beyond P13. The -Cu dams kept on treatment for this 3-wk period were killed and compared biochemically with +Cu dams and to nonpregnant females that were kept on the +Cu or -Cu treatment and fed the same diet for 3 wk. Compared with +Cu dams, -Cu dams had 48% lower hematocrits, 89% lower plasma ceruloplasmin activities, 45% lower liver copper level, and > 2-fold higher liver iron concentration. The -Cu, nonpregnant female mice did not differ in any of these copper status indicators from the +Cu dams or nonpregnant, +Cu females. When -Cu treatment was delayed until embryonic d 19, all -Cu pups survived weaning. Additional studies should be conducted to establish the human copper requirement for perinatal development and determine whether the 11 and 44% extra copper intakes recommended for pregnancy and lactation in the new United States recommended dietary allowance are sufficient.