title: The role of PPARγ in TBBPA-mediated endocrine disrupting effects in human choriocarcinoma JEG-3 cells.
abstract: The goal of the present study was to investigate the action of TBBPA on PPARγ protein expression in vitro in human choriocarcinoma-derived placental JEG-3 cells. We also analyzed TBBPA for its action on placental secretion of progesterone and β-hCG, cell viability, and apoptosis. Our results showed that after TBBPA treatment at 10 nM and 10 µM, PPARγ protein expression increased in a time-dependent manner until 48 h and then slightly decreased at 72 h but was still above the control level. This alteration in PPARγ protein expression was accompanied by a decreased β-hCG level. Interestingly, co-treatment with the PPARγ antagonist GW9662 reversed the TBBPA-mediated changes in PPARγ protein expression but, according to β-hCG secretion, potentiated an inhibitory effect of TBBPA. Additionally, in our study, we assessed the ability of TBBPA to increase progesterone levels in JEG-3 cells compared with those of controls. Finally, in the present study, we demonstrated that TBBPA at all of the tested doses significantly increased caspase-3 activity compared with that of the vehicle control. The apoptotic action of TBBPA was also confirmed by Hoechst 33342 staining. These results showed the up-regulation of PPARγ protein expression after TBBPA exposure in human placental cells. Although co-treatment with antagonist of PPARγ reversed the TBBPA-mediated increase in this protein expression and restored it to the control level, it did not reverse the effect on β-hCG secretion. This indicated that the mechanism of TBBPA-induced changes in β-hCG secretion is PPARγ-independent.
authors.affiliation: Department of Animal Biotechnology, University of Agriculture, Rędzina 1B, 30-248, Kraków, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Honkisz
authors.affiliation: Department of Animal Biotechnology, University of Agriculture, Rędzina 1B, 30-248, Kraków, Poland. anna.wojtowicz@ur.krakow.pl.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Wójtowicz
mesh_terms: D000813:Anilides / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001577:Benzophenones / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002822:Choriocarcinoma / Q000503:physiopathology*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000378:metabolism*; D052244:Endocrine Disruptors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014594:Uterine Neoplasms / Q000503:physiopathology*
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D001577:Benzophenones; D018997:Chorionic Gonadotropin, beta Subunit, Human; D052244:Endocrine Disruptors; D047495:PPAR gamma; D011075:Polybrominated Biphenyls; D014443:Tyrosine; D011374:Progesterone; D053148:Caspase 3; C020806:tetrabromobisphenol A; C120099:GW 1929
keywords: Caspase-3; JEG-3; Peroxisome proliferator-activated receptor gamma; Progesterone; Tetrabromobisphenol A; β-hCG