Lack of ceruloplasmin expression alters aspects of copper transport to the fetus and newborn, as determined in mice

Abstract

Copper transport and accumulation were studied in virgin and lactating C57BL/6 mice, with and without expression of ceruloplasmin (Cp), to assess the importance of Cp to these processes. One hour after i.p. injection of tracer (64)Cu, liver and kidney accounted for 80% of the radioactivity, and mammary gland 1%, while in lactating Cp+/+ mice 2-4 days post partum, uptake by mammary gland was 9-fold higher and that of liver and other organs was decreased, with (64)Cu rapidly appearing in milk. Parallel studies in Cp-/- mice (siblings from same colony) gave virtually identical results. However, their milk contained less (64)Cu, and actual copper contents determined by furnace atomic absorption were less than half those for milk from normal dams. Liver copper concentrations of pups born to Cp-/- dams also were half those of pups from wild type dams. Copper in pup brains was unaffected; but iron concentrations were reduced. We conclude that absence of Cp, while not affecting entry of exchangeable copper from the blood into the mammary gland, does have a significant effect on the availability of this metal to the newborn through the milk and in the form of stores accumulating in gestation.

Maternal choline modifies fetal liver copper, gene expression, DNA methylation, and neonatal growth in the tx-j mouse model of Wilson disease

“…Addressing these four main observations, first, the finding of low Cu concentrations in tx-j fetal livers can be attributed to the low circulating serum ceruloplasmin in untreated tx-j dams with consequent lack of placental Cu transport. 25 Importantly, we observed that fetal liver Cu concentrations in the tx-j strain were even lower in the maternal choline supplemented than in the control diet group. In our previous study on adult tx-j mice, we found that betaine, a methyl group donor product of choline metabolism, was associated with reduced hepatic Cu concentration as well.…”

Serum depletion of holo-ceruloplasmin induced by silver ions in vivo reduces uptake of cisplatin

“…Replacement of copper atoms associated with Cp with silver atoms makes Cp misfolded and enzymatically inactive. Possibly, the copper transporting function of Cp [40][41][42] is lost as well. Thus, the state induced by AgCl-containing diet may be viewed as a model of adult mammals with low copper status without manifested toxic effects.…”

Iron deficiency during pregnancy: the consequences for placental function and fetal outcome

“…In support of the latter hypothesis, possible receptors have been identified in tissues such as placenta (14) and copper from ceruloplasmin can be donated to the fetus in pregnancy (13) . However, it is not essential for this function, because individuals who carry a mutation that results in absence of ceruloplasmin do not show symptoms of copper deficiency.…”