Bisphenol A induces apoptosis and G2-to-M arrest of ovarian granulosa cells.
We investigated the impact of bisphenol A (BPA) on murine ovarian granulosa cells. Ovarian granulosa cells were cultured with 100 fM to 100 microM BPA for 24 h to 72 h. BPA decreased granulosa cell viability in a dose- and time-dependent manner. The lowest concentration that induced a significant decrease was 100 pM (89.2 +/- 4.0% of the control). TUNEL analysis demonstrated that treatment with BPA increased apoptosis of granulosa cells in a dose- and time-dependent manner. In addition, flow cytometry analyses revealed that treatment with BPA resulted in G2-to-M arrest, which was most prominent at 48 h. BPA increased the expression of Bax and concomitantly decreased the expression of Bcl2 at both protein and mRNA levels of granulosa cells. These findings suggest that low, presumably environmentally relevant doses of BPA, decrease the viability of granulosa cells by inducing apoptosis and G2-to-M arrest. Up-regulation of Bax and down-regulation of Bcl2 were suggested to be involved in this apoptotic effect.
Xu
Jiping
J
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Osuga
Yutaka
Y
Yano
Tetsu
T
Morita
Yutaka
Y
Tang
Xiaohui
X
Fujiwara
Toshihiro
T
Takai
Yasushi
Y
Matsumi
Hirotaka
H
Koga
Kaori
K
Taketani
Yuji
Y
Tsutsumi
Osamu
O
D000818:Animals; D017209:Apoptosis; D001559:Benzhydryl Compounds; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry; D016195:G2 Phase / Q000187:drug effects; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007211:Indoles / Q000737:chemistry; D007700:Kinetics; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D005456:Fluorescent Dyes; D007211:Indoles; D010636:Phenols; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C494827:Bax protein, mouse; C007293:DAPI; C006780:bisphenol A; D000098826:Bisphenol A Compounds