Increased expression of Leydig cell haem oxygenase-1 preserves spermatogenesis in varicocele.
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.
Shiraishi
K
K
Department of Urology, Yamaguchi University School of Medicine, Japan. koji-shiraishi@uiowa.edu
Naito
K
K
D000328:Adult; D000447:Aldehydes / Q000378:metabolism; D001706:Biopsy; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D007985:Leydig Cells / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D013091:Spermatogenesis / Q000502:physiology*; D014646:Varicocele / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*
D000447:Aldehydes; D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C027576:4-hydroxy-2-nonenal