Placental copper transport in the rat: role of low-molecular-weight ligands.
In this study we investigated whether two low-molecular-weight (LMW) ligands with high affinity for copper (Cu) play a role in the transplacental transport of Cu in the rat. Dams on days 20-21 of gestation were anesthetized and injected via the femoral vein with 5 mg/kg (79 mumol/kg) Cu in 0.5 ml, as either the acetate [Cu(AcO)2], as a 1;10 mixture with L-histidine [Cu(His)10], or as the Cu-(glycyl-glycyl-L-histidine) [G-G-H] complex. Controls received saline. After laparotomy, several fetuses and their placentas were removed at 0, 10, 20, 40, and 60 min after injection, simultaneously with dam blood. Peak Cu concentration in dam plasma occurred at 10 min and was highest following Cu(AcO)2 injection. At 10 and 20 min the placentas from the Cu(AcO)2 and the Cu(G-G-H) groups had higher Cu levels than the controls. By 40 min placentas from all rats injected with Cu had similar Cu concentrations. In the Cu(AcO)2 group there was a positive correlation between dam plasma and placental Cu (r = 0.527, P < 0.05). A sharp downhill gradient was observed between dam and fetus. Fetal plasma Cu levels did not differ among all groups at any time. The data indicate that LMW ligands do not enhance overall maternal-to-fetal Cu transfer, but that an excess of His may inhibit the release of Cu from placenta to fetus.