Effect of ABCB4 protein in the placenta of rat with low level cadmium exposure / 中国职业医学

ABSTRACT

OBJECTIVE: To gain insight into the effect associated with cadmium toxicity in placenta and explore the reproductive toxicity of low level cadmium exposure. METHODS: Thirty-two specific pathogen free healthy female SD rats were randomly divided into 4 groups with 8 rats in each group. These were a control group and low-,medium- and highcadmium treated groups. Rats were treated with 0,1,3,9 mg / kg body weigh( bw) cadmium chloride by intragastric administration respectively. The treatment was once a day for 43 consecutive days as the one-generation reproductive toxicity experiment. On gestation day 20,the parental females were euthanized or delivered. The numbers of corpus luteum,implantations,live or dead fetuses,resorptions were all recorded and represented as reproductive toxicity index.Some placentas were prepared for proteomic analysis with difference gel electrophoresis method, some for histological analysis,some were analyzed by Western blot and immunohistochemistry methods. RESULTS: There was no statistical significance between low-cadmium treated group and control group in the changes of the body weights and reproductive toxicity index( P > 0. 05). The female rats showed different degrees of slow body weights gain from gavages day 19 in medium-and high-cadmium treated groups. According to the proteomic screening criteria in placenta,15 protein spots with a 1. 5-fold change relative to the controls in medium- and high-cadmium treated groups were identified. To validate the proteomics results,ATP-binding cassette,sub-family B,member 4( ABCB4) was examined by Western blot. The result showed that the expression of ABCB4 was significantly down-regulated in the cadmium treated groups( P < 0. 05).Moreover,there was a dose-response relationship between cadmium exposure and ABCB4 protein expressions( P < 0. 05).The histological analysis of placenta showed an increasing tendency towards degradation of cytotrophoblastic cells,hyperemia and decreased glycogen cells with increasing cadmium exposure. The subcellular localization of ABCB4 protein was mainly in the nucleus or cytoplasm in placenta. CONCLUSION: The above results demonstrated that the exposure to 1mg / kg· bw · d cadmium had not significant reproductive toxicity. The placenta is a target organ of cadmium toxicity.ABCB4 protein maybe involved in mediating the toxicity of cadmium in placenta.