Bisphenol A inhibits cell viability and differentiation in micromass culture of rat embryonic midbrain cells via the Notch-Hes pathway
10.3867/j.issn.1000-3002.2014.02.005
- VernacularTitle:双酚A抑制大鼠胚胎中脑微团细胞的存活和分化与Notch-Hes通路有关
- Author:
Ran LIU
;
Jianjun JIANG
;
Lanqin SHANG
;
Xuetao WEI
;
Shuang WU
;
Weidong HAO
- Publication Type:Journal Article
- Keywords:
bisphenol A;
micro mass culture;
estrogen receptor;
cell viability;
cell differentiation
- From:
Chinese Journal of Pharmacology and Toxicology
2014;(2):175-181
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE Study the role of estrogen receptor (ER)in the inhibition of cell viability and differentiation induced by bisphenol A (BPA)in micro mass culture of rat e mbryonic midbrain(MB) cells.METHODS Micro mass cultures of MB were prepared fro m rat e mbryonic midbrain on gestation day 13.MB cells were exposed to BPA (10 -4 ,10 -6 ,10 -8 ,10 -10 ,10 -12 mol·L -1 )for 5 d.Cell viability was assessed by neutral red uptake test.MB differentiation was detected by he matoxylin staining and i mage analysis.In order to observe the role of ER pathway in the toxicity induced by BPA,cell cultures were co-treated with ICI182780 0.1 n mol·L -1 ,ta moxifen 1 n mol·L -1 and BPA 0.1 mmol·L -1 for 5 d, the cell viability and foci differentiation were detected.Moreover,the protein expression levels of ER in normal e mbryonic brain of gestation day 18,testis tissue fro m adult rats and midbrain cells untreated with BPA were investigated by Western blot.The mRNA expression levels of ER in normal e mbryonic brain of gestation day 13 and gestation day 18,ovary and testis tissue fro m adult rats,and midbrain cells un-treated with BPA were investigated by real-ti me PCR.The mRNA expression levels of Notch1 and Hes1 in MB cells treated with BPA 0.1 mmol·L -1 were also detected by real-ti me PCR.RESULTS BPA 0.1 mmol·L -1 could inhibited MB cell viability and foci differentiation.However,this effect could not be reversed by ER antagonist.The protein and mRNA expression levels of ER in e mbryonic brain and MB cells untreated with BPA were found to be extre mly low.In addition,BPA 0.1 mmol·L -1 could inhibited the mRNA expression levels of Notch1 and Hes1 .CONCLUSION BPA could inhibited MB cell viability and foci differentiation.ER pathway might be not involved in this effect.Instead,Notch-Hes pathway might be involved for this effect.
