title: Soy isoflavones administered to rats from weaning until sexual maturity affect ovarian follicle development by inducing apoptosis.
abstract: Twenty-one-day-old female Wistar rats were treated daily with orally administered soy isoflavones (SIFs) at concentrations of 50, 100, or 200 mg/kg body weight from weaning until sexual maturity (3 mo.), and ovarian follicle development was evaluated. At the end of the treatment period, the ultrastructure of the ovarian granulosa cells was examined by transmission electron microscopy. The apoptotic cell death of ovarian granulosa cells was detected using TUNEL staining. The mRNA expression levels of caspase-3, caspase-8, caspase-9, Bcl2, Bax, and Fas were determined by real-time quantitative PCR. The protein expression levels of caspase-3, Bcl2, Bax, and Fas were determined by western blotting. Our data showed that exposure to SIFs resulted in morphological changes consistent with ovarian granulosa cell apoptosis. The percentage of TUNEL-positive granulosa cells was increased. The mRNA expression levels of the apoptosis-related genes caspase-3, caspase-8, caspase-9, Bax, and Fas increased significantly. The protein levels of Bax, Fas, and cleaved caspase-3 were also increased. These results indicate that the exposure of rats to modest doses of SIFs from weaning until sexual maturity can affect ovarian follicle development by inducing apoptosis. The mechanism of SIF-induced alterations in ovarian follicle development may involve the activation of Fas-mediated and Bcl2/Bax-mediated apoptotic signaling pathways.
authors.affiliation: Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China; Fujian Province Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Wang
authors.affiliation: Center for Reproductive Medicine, Teaching Hospital of Fujian Medical University, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Fujian Province Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Fujian Province Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Fujian Province Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China; Department of Pharmacy, College of Fujian Health, Fuzhou, Fujian, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Fujian Province Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Shihua
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Fujian Province Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Shaozheng
authors.initials: S
authors.lastname: Weng
authors.affiliation: Fujian Province Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China. Electronic address: wenchang2002@sina.com.
authors.forename: Wenchang
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D019833:Genistein / Q000097:blood; D006107:Granulosa Cells / Q000187:drug effects* / Q000648:ultrastructure; D020287:In Situ Nick-End Labeling; D007529:Isoflavones / Q000097:blood / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D045730:Soy Foods / Q000032:analysis*; D014886:Weaning; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; C491898:Fas protein, rat; D007529:Isoflavones; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; C004742:daidzein; D019833:Genistein; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9
keywords: Apoptosis; Follicle; Ovary; Phytoestrogens; Soy isoflavones