title: Bisphenol A induces apoptosis and G2-to-M arrest of ovarian granulosa cells.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Jiping
authors.initials: J
authors.lastname: Xu
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Osuga
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yano
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Morita
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Tang
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takai
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsumi
authors.forename: Kaori
authors.initials: K
authors.lastname: Koga
authors.forename: Yuji
authors.initials: Y
authors.lastname: Taketani
authors.forename: Osamu
authors.initials: O
authors.lastname: Tsutsumi
mesh_terms: 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
chemical_list: 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