• PMID: 16834661
• Gene Name: NR5A1
• Condition: Infertility
• Association: The study concludes that Ad4 BP/SF-1 is important for the maintenance of steroidogenesis in the human testis
• Population size: 30
• Population details: 22 patients, 8 controls
• Age: Patients (Mean age: 33.1 ± 7.6 years ), Control (1 - 26 yrs)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: non-obstructive azoospermia, hypospermatogenesis, maturation arrest, Sertoli cell-only syndrome

Role of transcription factors Ad4bp/SF-1 and DAX-1 in steroidogenesis and spermatogenesis in human testicular development and idiopathic azoospermia

Kojima Y, Sasaki S, Hayashi Y, Umemoto Y, Morohashi K, Kohri K.

BACKGROUND: Ad4bp/SF-1 and DAX-1 are orphan members of the nuclear hormone receptor superfamily of transcription factors. In order to obtain better understandings of human testicular steroidogenesis and spermatogenesis, we examined the expression levels of both factors in human normal and idiopathic azoospermic testes and investigated their physical meaning. METHODS: First, we examined the expression level of Ad4bp/SF-1 and DAX-1 by quantitative reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry and western blotting analysis using eight normal human testicular tissues from infants to adults. Second, we performed quantitative RT-PCR using testicular biopsy samples obtained from 22 idiopathic azoospermic patients to examine the expression of Ad4bp/SF-1 and DAX-1, and analysed the correlation between the expression levels of both factors and the serum hormone levels or histological evaluation to study their potential correlation with steroidogenesis and spermatogenesis on idiopathic azoospermia. RESULTS: The expression levels of both factors in the normal testes increased with testicular development. Ad4bp/SF-1 was abundantly expressed in Leydig cell, whereas DAX-1 was expressed in Sertoli cells. The expression level of Ad4bp/SF-1 in idiopathic azoospermic patients testes positively correlated with serum testosterone (P < 0.05). The average expression levels of DAX-1 mRNA for patients with maturation arrest (0.39 +/- 0.19) and Sertoli cell-only syndrome (0.13 +/- 0.08) were lower than that with hypospermatogenesis (1.60 +/- 1.32) and normal spermatogenesis (1.30 +/- 1.41). CONCLUSION: Ad4bp/SF-1 is important for the maintenance of steroidogenesis in the human testis. DAX-1 plays a critical role in spermatogenesis in the human testis, and Sertoli cell-only syndrome and maturation arrest may result from abnormal Sertoli cell function that disrupts the normal progression of spermatogenesis. FAU - Kojima, Yoshiyuki AU - Kojima Y AD - Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. ykojima@med.nagoya-cu.ac.jp FAU - Sasaki, Shoichi AU - Sasaki S FAU - Hayashi, Yutaro AU - Hayashi Y FAU - Umemoto, Yukihiro AU - Umemoto Y FAU - Morohashi, Ken-Ichiro AU - Morohashi K