Elevated scrotal temperature, but not varicocele grade, reflects testicular oxidative stress-mediated apoptosis

Elevation of scrotal temperature has been known as a cause of male infertility but the exact mechanism leading to impaired spermatogenesis is unknown. This work aimed to investigate the role of elevated scrotal temperature, oxidative stress, and apoptosis in testes of infertile males associated with varicocele. Thirty-two testicular biopsies from patients with left varicocele who underwent preoperative measurement of scrotal temperature (Delta T), serum follicle stimulating hormone (FSH), luteinizing hormone, and testosterone were included. Generation of 4-hydroxy-2-nonenal (4-HNE)-modified proteins and proteolytic fragments of poly(ADP-ribose) polymerase (PARP) and caspase-3 detected by Western blotting were examined as markers for oxidative stress and apoptosis, respectively. These expressions were compared with clinical parameters. Irrespective of varicocele grades, sperm concentration, motility, serum FSH, and testosterone were deteriorated with the increase of Delta T. There was a distinct correlation between generation of 4-HNE-modified proteins and Delta T, indicating a close association between scrotal temperature and oxidative stress. Cleavages of PARP and caspase-3, which appear at 86 and 17 kDa, respectively, were strongly correlated with Delta T and generation of 4-HNE-modified proteins. Elevation of scrotal temperature is one of the major factors to impair spermatogenesis and steroidogenesis in testis with varicocele. This heat stress is shown to be closely associated with oxidative stress, following the apoptosis of germ cells.