2011 ROLE OF TRANSCRIPTION FACTOR DAX-1 AS A NEW FUNCTIONAL MARKER OF UNDIFFERENTIATED SERTOLI CELLS IN AZOOSPERMIA PATIENTS

Abstract

You have accessJournal of UrologyInfertility: Physiology, Pathophysiology, Basic Research1 Apr 20112011 ROLE OF TRANSCRIPTION FACTOR DAX-1 AS A NEW FUNCTIONAL MARKER OF UNDIFFERENTIATED SERTOLI CELLS IN AZOOSPERMIA PATIENTS Yoshiyuki Kojima, Yutaro Hayashi, Kentaro Mizuno, Yukihiro Umemoto, Shoichi Sasaki, and Kenjiro Kohri Yoshiyuki KojimaYoshiyuki Kojima Nagoya, Japan More articles by this author , Yutaro HayashiYutaro Hayashi Nagoya, Japan More articles by this author , Kentaro MizunoKentaro Mizuno Nagoya, Japan More articles by this author , Yukihiro UmemotoYukihiro Umemoto Nagoya, Japan More articles by this author , Shoichi SasakiShoichi Sasaki Nagoya, Japan More articles by this author , and Kenjiro KohriKenjiro Kohri Nagoya, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2239AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES DAX-1 is an orphan member of the nuclear hormone receptor superfamily and acts as a transcriptional repressor. It plays a critical role in gonadal function and steroidogenesis. The characterization of Dax-1-deficient male mice suggested that Dax1 plays an important role in the maintenance of spermatogenesis. In our study, we examined the expression levels of DAX-1 in several azoospermiac patients with Sertoli cell-only testes and discuss the possibility of DAX-1 as a functional marker of undifferentiated Sertoli cells in azoospermia patients. METHODS All patients were diagnosed as Sertoli cell-only by histological observation. Ten idiopathic azoospermia patients with Sertoli cell-only syndrome, five azoospermia patients with cryptorchidism, and four azoospermia patients with hypogonadropic hypogonadism were enrolled. Five obstructive azoospermia patients with normal spermatogenesis were included as additional testicular samples. We performed immunohistochemical study and quantitiative RT-PCR using testicular biopsy samples to examine the DAX-1 expression, and analyzed the role of DAX-1 in Sertoli cells. In addition, transcriptional activities of DAX-1 by FSH stimulation were examined with TM4 derived from mouse testicular Sertoli cells. RESULTS Immunohistochemical study showed that DAX-1 was strongly expressed in the nuclei of Sertoli cells in patients with cryptorchidism, hypogonadropic hypogonadism or normal spermatogenesis. On the other hand, it was faintly expressed in the nuclei of Sertoli cell in patients with idiopathic azoospermia. The average expression levels of DAX-1 mRNA in idiopathic azoospermia patients with Sertoli cell-only syndrome (0.13±0.08) were lower than those with cryptorchidism (1.38±0.37), hypogonadropic hypogonadism (0.98±0.34) or normal spermatogenesis (1.30±1.41). Identical amounts of DAX1 were detected regardless of FSH stimulation in TM4 cells, and DAX1 was not activated significantly by FSH with TM4. CONCLUSIONS These results suggest that the function of DAX-1 in Sertoli cells may be required for normal spermatogenesis and fertility. Idiopathic azoospermia may result in abnormal Sertoli cell function, which disrupts the normal progression of spermatogenesis. Transcription of the DAX-1 gene may be negatively regulated by factors other than FSH, especially in Sertoli cells in Sertoli cell-only syndrome. Given the essential role of DAX-1 in Sertoli cells with normal spermatogenesis, its defect could reflect a new functional marker of undifferentiated Sertoli cells. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e804-e805 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yoshiyuki Kojima Nagoya, Japan More articles by this author Yutaro Hayashi Nagoya, Japan More articles by this author Kentaro Mizuno Nagoya, Japan More articles by this author Yukihiro Umemoto Nagoya, Japan More articles by this author Shoichi Sasaki Nagoya, Japan More articles by this author Kenjiro Kohri Nagoya, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...