Effects of arsenite on the expression of estrogen receptor gene and the ER signaling pathway in rats / 中华地方病学杂志

ABSTRACT

Objective To explore the effects of arsenite on the expression of estrogen receptor (ER) mRNA,ER protein and the ER signaling pathway in rats.Methods Random grouping experiment design was used to evaluate the effects of arsenite on the expression of ER mRNA,ER protein and the ER signaling pathway (24 rats were divided into 4 groups:control,Aslow,Asmiddle,Ashigh groups;6 rats in each group).Female rats were exposed to NaAsO2 (0.625,2.500,10.000 mg/kg) by oral perfusion at gradient doses for three months respectively.The expression of ER mRNA as effect biomarker was observed through RT-PCR.The concentration of ER,vascular endothelial growth factor (VEGF),cyclin D1 (CYC-D1),and progesterone receptor (PR) in serum was determined as effect biomarkers using enzyme-linked immunosorbent assay (ELISA).Results The levels of ER mRNA,VEGF,PR,CYC-D1,and ER in control,Aslow,Asmiddle,and Ashigh groups were statistically different (F =204.13,227.14,256.13,179.23,167.34,all P ＜ 0.01).With increasing of arsenic,the expression of ER mRNA,VEGF,and PR gradually decreased (all P ＜ 0.01);the dose effect relationship was obvious;the expression of CYC-D1 and ER in Asmiddle [(25.45 ± 9.29) U/L,(22.16 ± 9.16) ng/L] was higher than that in Ashigh [(2.60 ± 0.23) U/L,(9.06 t 2.06) ng,/L,all P ＜ 0.01].Arsenic was negatively associated with ER mRNA,ER,VEGF,CYC-D1 and PR (r =-0.689,-0.515,-0.675,-0.456,-0.397,P ＜ 0.01 or ＜ 0.05).ER mRNA was positively associated with ER,VEGF,CYC-D1 and PR (r =0.894,0.662,0.713,0.699,P ＜ 0.01 or ＜ 0.05).Conclusions The expression of ER mRNA and ER protein are inhibited by arsenic,ER may be served as a sensitive biomarker of reproductive system damage after exposed to arsenic.The ER-VEGF,CYC-D1 and PR pathway participate in the process of reproductive system damage caused by arsenic.Arsenic is probably a environmental estrogen.