Placental copper transport in the rat. III: Interaction between copper and iron in maternal protein deficiency

Copper (Cu) and iron (Fe) metabolism are linked in the haematopoietic process. There is also considerable evidence of a linkage between protein intake and mineral sufficiency. The present study tested the hypothesis that a low protein diet during the second half of gestation in the rat alters Cu and Fe transport across the placenta and affects the Cu and Fe status of the fetus. Pregnant rats were fed a normal commercial diet the first half of gestation, and then assigned either a 20 per cent protein (NP) or a 4 per cent protein diet (LP) during the second half of gestation. One day before delivery, rats were anaesthetized, fetuses removed and dam tissues and plasma obtained. Other pregnant rats were injected i.v. with 2.5 mg/kg Cu acetate and sequential samples of dam blood, fetal blood and placentae were taken from 0 to 60 min. The LP diet produced generalized maternal hypoproteinaemia, and although there was no difference in fetal plasma albumin, there was a generalized fetal hypoproteinaemia as well. Fetal haematocrit (Hct) of the LP litters was lower than that of the NP group, but dam Hct was unchanged. Dam plasma Fe and Cu showed no differences between diets. Dam liver Cu was unaltered but liver Fe stores were elevated significantly. Before and after a Cu bolus, the LP placentae retained Cu to a greater extent than those of the NP placentae. Fetal liver Cu and Fe were elevated in the LP litters compared to the NP group. In conclusion, the LP diet in the dam during the second half of gestation was associated with fetal anaemia, hypoproteinaemia, and increased Cu and Fe accumulation in fetal liver. The higher concentration of Cu and Fe retained in LP placentae during gestation, and confirmed in the Cu challenge, suggest that Cu and Fe delivery to the fetus is related to placental concentration and that maternal protein malnutrition is a regulatory factor in fetal mineral homeostasis.