title: Testosterone induces redistribution of forkhead box-3a and down-regulation of growth and differentiation factor 9 messenger ribonucleic acid expression at early stage of mouse folliculogenesis.
abstract: Increasing evidence has shown that excess androgen may be a main cause of polycystic ovary syndrome (PCOS). However, the molecular mechanism of androgen action on the ovary is unclear. To investigate the possible impacts of androgen on early follicular development, neonatal mouse ovaries mainly containing primordial follicles were cultured with testosterone. We demonstrated that the number of primary follicles was increased after 10 d culture with testosterone treatment via phosphatidylinositol 3-kinase/Akt pathway. Androgen induced Forkhead box (Foxo)-3a activation, and translocation of Foxo3a protein from oocyte nuclei to cytoplasm, which might be a key step for primordial follicle activation. Interestingly, testosterone was also capable of down-regulating growth and differentiation factor-9 expression via its receptor. In summary, we infer that intraovarian excess androgen in PCOS might result in excess early follicles by inducing oocyte Foxo3a translocation and follicular arrest by down-regulating growth and differentiation factor-9 expression.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Yang
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Huang
authors.forename: Shao-Yang
authors.initials: SY
authors.lastname: Ji
authors.forename: Cui-Ling
authors.initials: CL
authors.lastname: Lu
authors.forename: Cui-Hong
authors.initials: CH
authors.lastname: Fan
authors.forename: Huan
authors.initials: H
authors.lastname: Cai
authors.forename: Yu
authors.initials: Y
authors.lastname: Ren
authors.forename: Zhao-Yuan
authors.initials: ZY
authors.lastname: Hu
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Yi-Xun
authors.initials: YX
authors.lastname: Liu
mesh_terms: D000728:Androgens / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D017931:DNA Primers; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D055429:Growth Differentiation Factor 9 / Q000235:genetics*; D051543:Hepatocyte Nuclear Factor 3-gamma / Q000502:physiology*; D008297:Male; D051379:Mice; D006080:Ovarian Follicle / Q000166:cytology / Q000502:physiology; D010053:Ovary / Q000166:cytology / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D010766:Phosphorylation; D010957:Plasmids; D011085:Polycystic Ovary Syndrome / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D013737:Testis / Q000502:physiology; D013739:Testosterone / Q000494:pharmacology* / Q000502:physiology
chemical_list: D000728:Androgens; D017931:DNA Primers; C496506:Foxa3 protein, mouse; C525898:Gdf9 protein, mouse; D055429:Growth Differentiation Factor 9; D012333:RNA, Messenger; D051543:Hepatocyte Nuclear Factor 3-gamma; D013739:Testosterone; D051057:Proto-Oncogene Proteins c-akt