Hum. Reprod. Advance Access originally published online on May 5, 2005
Human Reproduction 2005 20(9):2608-2613; doi:10.1093/humrep/dei063
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Increased expression of Leydig cell haem oxygenase-1 preserves spermatogenesis in varicocele
Department of Urology, Yamaguchi University School of Medicine, Japan
1 To whom correspondence should be addressed at: Department of Pharmacology, University of Iowa, 2-310 Bowen Science Building, 51 Newton Road, Iowa City, IA 52242, USA. Email: koji-shiraishi{at}uiowa.edu.
BACKGROUND: Oxidative stress is involved in the pathogenesis of testicular disorders. Haem oxygenase-1 (HO-1) plays an important cytoprotective role against oxidative stress. We investigated the presence of oxidative stress, represented by generation of 4-hydroxy-2-nonenal (4-HNE)-modified proteins, and expression of HO-1 in varicocele testes of human. METHODS: Thirty testicular biopsies from patients with left varicocele and 10 from patients with normal spermatogenesis were included. Generation of 4-HNE-modified proteins was examined as a marker of oxidative stress. Expression of HO-1 was assessed by western blotting and immunohistochemistry. The expression was compared with clinico-pathological parameters. RESULTS: Increased generation of 4-HNE-modified proteins was observed in varicocele testes. HO-1 expression was significantly correlated with varicocele grade (P<0.01 in grade 2 and 3 compared to control) and expression of 4-HNE-modified proteins (r=0.508, P<0.01). The immunoreactivity was increased in Leydig cells in varicocele testes. There were significant correlations between age, total motile sperm count, Johnsen's mean score and HO-1:4-HNE-modified protein ratio (r=0.206, 0.405 and 0.408, P=0.027, 0.027 and 0.025 respectively). CONCLUSIONS: In testes with varicocele, there are increases in 4-HNE-modified proteins, suggesting that oxidative stress is present. Increased HO-1 expression, mainly in Leydig cells, is considered to protect the cells against oxidative stresses in varicocele testes.
Key words: haem oxygenase-1/human/oxidative stress/varicocele