PD8-12 DISTINCTIVE CHANGES IN HISTONE H3K4 MODIFICATION MEDIATED VIA KDM5A EXPRESSION IN SPERMATOGONIAL STEM CELLS OF CRYPTORCHID TESTES

You have accessJournal of UrologyStem Cell Research1 Apr 2014PD8-12 DISTINCTIVE CHANGES IN HISTONE H3K4 MODIFICATION MEDIATED VIA KDM5A EXPRESSION IN SPERMATOGONIAL STEM CELLS OF CRYPTORCHID TESTES Hidenori Nishio, Yutaro Hayashi, Yoshinobu Moritoki, Hideyuki Kamisawa, Satoshi Kurokawa, Akihiro Nakane, Kentaro Mizuno, Tetsuji Maruyama, Yoshiyuki Kojima, and Kenjiro Kohri Hidenori NishioHidenori Nishio More articles by this author , Yutaro HayashiYutaro Hayashi More articles by this author , Yoshinobu MoritokiYoshinobu Moritoki More articles by this author , Hideyuki KamisawaHideyuki Kamisawa More articles by this author , Satoshi KurokawaSatoshi Kurokawa More articles by this author , Akihiro NakaneAkihiro Nakane More articles by this author , Kentaro MizunoKentaro Mizuno More articles by this author , Tetsuji MaruyamaTetsuji Maruyama More articles by this author , Yoshiyuki KojimaYoshiyuki Kojima More articles by this author , and Kenjiro KohriKenjiro Kohri More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.806AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Gonocytes differentiate into spermatogonial stem cells (SSCs), which make it possible to maintain spermatogenesis continuously throughout life. The attenuation of SSC activity in cryptorchid testes results in altered spermatogenesis and affects fertility. Further, microarray analysis have shown that lysine (K)-specific demethylase 5A (Kdm5a) is highly expressed in undescended testes compared with normal testes at 9 days postpartum (dpp) in juvenile rats. We aimed to elucidate the function of Kdm5a, a key epigenetic regulator expressed in the testes, on early spermatogenesis. METHODS Flutamide (7.5 mg/day) was injected into the abdomen of pregnant rats for 7 days during gestational days 14–20 to obtain offspring with undescended testes. Rats were divided into 3 groups: control, offspring with normal testes (no flutamide); DT, offspring with descended testes; and UDT, offspring with undescended testes. We assessed Kdm5a expression in these groups by quantitative RT-PCR and western blotting analyses. The localization of the expression was assessed by immunohistochemistry. We performed western blotting analysis to evaluate the H3K4 modification state. Further, Kdm5a transfection was performed in a GC-1 cell line to investigate the action of the genes related to spermatogenesis. RESULTS Kdm5a expression was significantly higher in the UDT group at 9 dpp than in the control and DT groups. Further, Kdm5a was localized in the nuclei of gonocytes, spermatogonia, and spermatocytes. H3K4me3/me2 expression levels were decreased in the UDT group at 9 dpp relative to the control and DT groups. Furthermore, Kdm5a overexpression in GC-1 cells led to increased Esr2, Neurog3, Pou5f1, Ret, and Thy1 expression. CONCLUSIONS Recent studies have revealed that not only genetic but also epigenetic regulation plays a role in spermatogenesis. Kdm5a and histone H3K4 me2/me3 expression was significantly higher and lower, respectively, in the UDT group at 9 dpp, a time point of transformation of gonocytes into SSCs in normal testis. Further, Kdm5a overexpression led to changes in the gene expression of Esr2, Neurog3, Pou5f1, Ret, and Thy1. Thus, Kdm5a, via epigenetic regulation of these genes, plays a role in the acquisition of SSC characteristics during transformation of gonocytes into SSCs. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e221 Peer Review Report Advertisement Copyright & Permissions© 2014MetricsAuthor Information Hidenori Nishio More articles by this author Yutaro Hayashi More articles by this author Yoshinobu Moritoki More articles by this author Hideyuki Kamisawa More articles by this author Satoshi Kurokawa More articles by this author Akihiro Nakane More articles by this author Kentaro Mizuno More articles by this author Tetsuji Maruyama More articles by this author Yoshiyuki Kojima More articles by this author Kenjiro Kohri More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...