Participation of metal transporters in cadmium transport from mother rat to fetus

Abstract

The mechanism of cadmium transport from mother to fetus remains unclear. In this study, we examined the roles of the metal transporters DMT1, ZIP, and ZnT and the metal-binding protein metallothionein in the transport of Cd from mother to fetus in Cd-exposed rats. Cadmium (as CdCl(2)) was administered to female Wistar rats at doses of 0, 1, 2, or 5 mg Cd/kg/day via gastric tube daily for six consecutive days each week for 7 weeks. The concentration of Cd, Zn, and Cu in the uterus and the placenta were then determined. Uterine and placental expression of genes encoding iso-MTs (I, II, and III) and the metal transporters DMT1, ZIP8, ZIP14, ZnT1, ZnT2 and ZnT4 was determined using real-time PCR. The Cd concentration in the placenta and uterus increased with the Cd dose, while the concentration of Cu decreased. Cadmium accumulation in the uterus and placenta resulted in a increase in MT-II gene expression, suggesting that MT-II prevents Cd transport to the fetus by trapping Cd in the uterus and placenta. Expression of the genes encoding DMT1, ZIP14 and ZnT2 was upregulated in the placenta in a dose-dependent manner. Relatively high expression level of the ZnT4 gene than the other ZnT genes (ZnT1 and ZnT2) was observed in the uterus and the placenta. Our results suggest that in the placenta the metal transporters DMT1 and ZIP14 involved in the uptake of Cd into the cytosol.