Cadmium pathways during gestation and lactation in control versus metallothoinein 1,2-knockout mice

Effects of metallothionein (MT) on cadmium absorption and transfer pathways during gestation and lactation in mice were investigated. Female 129/SvJ metallothionein-knockout (MT1,2KO) and metallothionein-normal (MTN) mice received drinking water containing trace amounts of (CdCl2)-Cd-109 (0.15 ng Cd/ml; 0.074 muCi Cd-109/ml). Cd-109 and MT in maternal, fetal, and pup tissues were measured on gestation days 7, 14, and 17 and lactation day 11. In dams, MT influenced both the amount of Cd-109 transferred from intestine into body (two- to three-fold higher in MT1,2KO than MTN dams) and tissue-specific Cd-109 distribution (higher liver/kidney ratio in MT1,2KO dams). Placental Cd-109 concentrations in MT1,2KO dams were three- and seven-fold higher on gestation days 14 and 17, respectively, than in MTN dams. Fetal Cd-109 levels were low in both mouse types, but at least 10-fold lower in MTN fetuses. MT had no effect on the amount of Cd-109 transferred to pups via milk; furthermore, 85-90% of total pup Cd-109 was recovered in gastrointestinal tracts of both types, despite high duodenal MT only in MTN pups. A relatively large percentage of milk-derived intestinal Cd-109 was transferred to other pup tissues in both MT1,2KO and MTN pups (14 and 10%, respectively). These results demonstrate that specific sequestration of cadmium by both maternal and neonatal intestinal tract does not require MT. Although MT decreased oral cadmium transfer from intestine to body tissues at low cadmium exposure levels, MT did not play a major role in restricting transfer of cadmium from dam to fetus via placenta and to neonate via milk.