Modulation of estradiol synthesis and aromatase activity in human choriocarcinoma JEG-3 cells exposed to tetrabromobisphenol A

Abstract

The goal of the present study was to investigate the impact of tetrabromobisphenol A (TBBPA) on human choriocarcinoma-derived placental JEG-3 cells in vitro. We determined the effect of this compound on estradiol secretion, aromatase protein expression and activity in vitro in the JEG-3 cell line. We assessed the ability of TBBPA to increase intracellular levels of cAMP as well as its effect on cell viability and proliferation. Our results indicated that TBBPA, at a wide range of concentrations (1×10(-8)-5×10(-5)M), significantly induced estradiol secretion by JEG-3 cells compared to that of controls after 24, 48 or 72 h of exposure. This effect was accompanied by an increase in the aromatase protein expression in JEG-3 cells treated with 100 nM and 10 μM of TBBPA for 24 h. Additionally, in our study, we confirmed that TBBPA-induced changes in aromatase protein expression were associated w ith the up-regulation of aromatase activity and cAMP levels. No tested doses of TBBPA inhibited JEG-3 cell proliferation, except for the highest dose of 100 μM, which had a toxic effect on cell viability at all time points. The present study clearly indicates that TBBPA alters JEG-3 cells estrogen synthesis due to its action on CYP19 protein expression and thus this compound may interfere with normal placental development during early pregnancy.

Keywords: Aromatase; Cytotoxicity; Estradiol; JEG-3; Tetrabromobisphenol A; cAMP.