The apparent role of ATP7A in placenta and mammary epithelial cells before and after birth, as determined in transgenic (Tg) mice overexpressing the human transporter

Placenta and mammary epithelium contain both forms of the Cu “pump”, ATP7A and B, begging the question of their roles in these cells during pregnancy and lactation. Confocal microscopy indicates they have different cellular locations, 7A being on the basolateral (blood) side of the lactating mammary cell and 7B in the apical region. In human term placenta, 7A is still on the basolateral side ‐ in this case the fetal side of syncytiotrophoblasts, and 7B is more centrally located. We used Tg mice expressing hATP7A at 5–10x levels of endogenous Atp7a to test whether in the mammary epithelium it might serve to return Cu to the maternal blood and conversely would be rate limiting for materno‐fetal transfer of Cu by placenta. Transport studies with 64 Cu tracer and analyses of total Cu by furnace atomic absorption after wet ashing showed less than half as much Cu in mammary epithelium and milk 2–4days post partum, and a markedly reduced rate of Cu transport into milk and to pups. Data in pregnancy were less clear cut, total Cu in the Tg pups tending to be higher than wild type in most stages of pregnancy, but with no obvious difference in the rate of transfer of tracer 64 Cu 1h after injection into the dam, nor in pup Cu content at birth. Our findings lend clear support to the concept that ATP7A prevents excess Cu from entering the milk and suggest that it is not rate limiting for Cu transport to the fetus. Supported in part by US PHS Grant HD46949.