Effects of cadmium on the placental uptake and transport to the fetus of nutrients.

Cadmium (Cd) is known to produce malformations, growth inhibition of the fetus, and placental necrosis in rodents at higher doses (3-4 mg/kg body wt). We studied the influence of Cd in various doses (0.5-4 mg/kg body wt) and at different survival intervals on the placental uptake and transfer to the fetus of vitamin B12 (vit. B12), zinc (Zn), alpha-aminobutyric acid (AIB), and deoxyglucose (DOX). These were chosen to represent various mechanisms of membrane transport. We show that vit. B12, which is accumulated in the placenta by a presumed receptor-mediated mechanism, is most easily disturbed by Cd. Thus, a significant decrease in transfer to the fetus was seen already 1 h after a high dose (4 mg/kg body wt) of Cd, and also at longer intervals (24 h) after low doses (0.5 mg/kg body wt). The transport of Zn (chemically similar to Cd) was also disturbed, but its inhibition was probably due in part to a decreased maternal serum concentration. The transport of AIB and DOX was largely unaffected. We conclude that inhibition of nutrient transfer to the fetus may be the underlying mechanism of growth retardation and possibly of the malformations produced by Cd. Vitamin B12 may be a sensitive indicator of early and subtle disturbances of placental function, not only for Cd but also for other chemicals suspected of causing placental disturbances.