title: 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.
authors.affiliation: Department of Animal Biotechnology, University of Agriculture, Rędzina 1B, 30-248 Cracow, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Honkisz
authors.affiliation: Department of Animal Biotechnology, University of Agriculture, Rędzina 1B, 30-248 Cracow, Poland. Electronic address: anna.wojtowicz@ur.krakow.pl.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Wójtowicz
mesh_terms: D001141:Aromatase / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002822:Choriocarcinoma / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D000242:Cyclic AMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D005411:Flame Retardants / Q000633:toxicity*; D006801:Humans; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*
chemical_list: D052244:Endocrine Disruptors; D005411:Flame Retardants; D011075:Polybrominated Biphenyls; D004958:Estradiol; D000242:Cyclic AMP; D001141:Aromatase; C561410:CYP19A1 protein, human; C020806:tetrabromobisphenol A
keywords: Aromatase; Cytotoxicity; Estradiol; JEG-3; Tetrabromobisphenol A; cAMP