Skip to main content
Top
Published in: World Journal of Urology 3/2010

01-06-2010 | Original Article

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

Authors: Koji Shiraishi, Hiroshi Takihara, Hideyasu Matsuyama

Published in: World Journal of Urology | Issue 3/2010

Login to get access

Abstract

Purpose

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.

Methods

Thirty-two testicular biopsies from patients with left varicocele who underwent preoperative measurement of scrotal temperature (ΔT), 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.

Results

Irrespective of varicocele grades, sperm concentration, motility, serum FSH, and testosterone were deteriorated with the increase of ΔT. There was a distinct correlation between generation of 4-HNE-modified proteins and ΔT, 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 ΔT and generation of 4-HNE-modified proteins.

Conclusions

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.
Literature
1.
go back to reference Bujan LM (1995) Testicular heating and its possible contributions to male infertility: a review. Int J Androl 18:169–184CrossRefPubMed Bujan LM (1995) Testicular heating and its possible contributions to male infertility: a review. Int J Androl 18:169–184CrossRefPubMed
2.
go back to reference Jung A, Schuppe HC (2007) Influence of genital heat stress on semen quality in humans. Andrologia 39:203–215CrossRefPubMed Jung A, Schuppe HC (2007) Influence of genital heat stress on semen quality in humans. Andrologia 39:203–215CrossRefPubMed
3.
go back to reference Hjollund NHI, Storgaard L, Ernst E et al (2002) Impact of diurnal scrotal temperature on semen quality. Reprod Toxicol 16:215–221CrossRefPubMed Hjollund NHI, Storgaard L, Ernst E et al (2002) Impact of diurnal scrotal temperature on semen quality. Reprod Toxicol 16:215–221CrossRefPubMed
4.
go back to reference Yamaguchi M, Sakatoku J, Takihara H et al (1989) The application of intrascrotal deep body temperature measurement for the noninvasive diagnosis of varicocele. Fertil Steril 52:295–301PubMed Yamaguchi M, Sakatoku J, Takihara H et al (1989) The application of intrascrotal deep body temperature measurement for the noninvasive diagnosis of varicocele. Fertil Steril 52:295–301PubMed
5.
go back to reference Turner TT, Lysiak JJ (2008) Oxidative stress: a common factor in testicular dysfunction. J Androl 29:488–498CrossRefPubMed Turner TT, Lysiak JJ (2008) Oxidative stress: a common factor in testicular dysfunction. J Androl 29:488–498CrossRefPubMed
6.
go back to reference Köksal IT, Tefekli A, Usta M et al (2000) The role of reactive oxygen species in testicular dysfunction associated with varicocele. BJU Int 86:549–552CrossRefPubMed Köksal IT, Tefekli A, Usta M et al (2000) The role of reactive oxygen species in testicular dysfunction associated with varicocele. BJU Int 86:549–552CrossRefPubMed
7.
go back to reference Shiraishi K, Naito K (2005) Increased expression of Leydig cell heme oxygenase-1 preserves spermatogenesis in varicocele. Hum Reprod 20:2608–2613CrossRefPubMed Shiraishi K, Naito K (2005) Increased expression of Leydig cell heme oxygenase-1 preserves spermatogenesis in varicocele. Hum Reprod 20:2608–2613CrossRefPubMed
8.
go back to reference Shiraishi K, Naito K (2006) Generation of 4-hydroxy-2-nonenal modified proteins in testis predicts improvement in spermatogenesis after varicocelectomy. Fertil Steril 86:233–235CrossRefPubMed Shiraishi K, Naito K (2006) Generation of 4-hydroxy-2-nonenal modified proteins in testis predicts improvement in spermatogenesis after varicocelectomy. Fertil Steril 86:233–235CrossRefPubMed
9.
go back to reference Shiraishi K, Naito K (2007) Effects of 4-hydroxy-2-nonenal, a marker of oxidative stress, on spermatogenesis and expression of p53 protein in male infertility. J Urol 178:1012–1017CrossRefPubMed Shiraishi K, Naito K (2007) Effects of 4-hydroxy-2-nonenal, a marker of oxidative stress, on spermatogenesis and expression of p53 protein in male infertility. J Urol 178:1012–1017CrossRefPubMed
10.
11.
go back to reference Paul C, Teng S, Saunders PTK (2009) A single, mild, transient scrotal heat stress causes hypoxia and oxidative stress in mouse testes, which induces germ cell death. Biol Reprod 80:913–919CrossRefPubMed Paul C, Teng S, Saunders PTK (2009) A single, mild, transient scrotal heat stress causes hypoxia and oxidative stress in mouse testes, which induces germ cell death. Biol Reprod 80:913–919CrossRefPubMed
12.
go back to reference Jung A, Leonhardt F, Shill WB et al (2005) Influence of the type of undertrousers and physical activity on scrotal temperatures. Hum Reprod 20:1022–1027CrossRefPubMed Jung A, Leonhardt F, Shill WB et al (2005) Influence of the type of undertrousers and physical activity on scrotal temperatures. Hum Reprod 20:1022–1027CrossRefPubMed
13.
14.
go back to reference Wang C, Berman N, McDonald V et al (1997) Effect of increased scrotal temperature on sperm production in normal men. Fertil Steril 68:334–339CrossRefPubMed Wang C, Berman N, McDonald V et al (1997) Effect of increased scrotal temperature on sperm production in normal men. Fertil Steril 68:334–339CrossRefPubMed
15.
go back to reference Mieusset R, Bujan L, Mondinat C et al (1987) Association of scrotal hyperthermia with impaired spermatogenesis in infertile men. Fertil Steril 48:1006–1011PubMed Mieusset R, Bujan L, Mondinat C et al (1987) Association of scrotal hyperthermia with impaired spermatogenesis in infertile men. Fertil Steril 48:1006–1011PubMed
16.
go back to reference Zorgniotti AW, Sealfon AI (1998) Measurement of intrascrotal temperature in normal and subfertile men. J Reprod Fertil 82:563–566 Zorgniotti AW, Sealfon AI (1998) Measurement of intrascrotal temperature in normal and subfertile men. J Reprod Fertil 82:563–566
17.
go back to reference Ahotupa M, Huhtaniemi I (1992) Impaired detoxification of reactive oxygen and consequent oxidative stress in experimentally cryptorchid rat testis. Biol Reprod 46:1114–1118CrossRefPubMed Ahotupa M, Huhtaniemi I (1992) Impaired detoxification of reactive oxygen and consequent oxidative stress in experimentally cryptorchid rat testis. Biol Reprod 46:1114–1118CrossRefPubMed
18.
go back to reference Ikeda M, Kodama H, Fukuda J et al (1999) Role of radical oxygen species in rat testicular germ cell apoptosis induced by heat stress. Biol Reprod 61:393–399CrossRefPubMed Ikeda M, Kodama H, Fukuda J et al (1999) Role of radical oxygen species in rat testicular germ cell apoptosis induced by heat stress. Biol Reprod 61:393–399CrossRefPubMed
19.
go back to reference Benoff SH, Millan C, Hurley IR et al (2004) Bilateral increased apoptosis and bilateral accumulation of cadmium in infertile men with left varicocele. Hum Reprod 19:616–627CrossRefPubMed Benoff SH, Millan C, Hurley IR et al (2004) Bilateral increased apoptosis and bilateral accumulation of cadmium in infertile men with left varicocele. Hum Reprod 19:616–627CrossRefPubMed
20.
go back to reference Cam K, Simsek F, Yuksel M et al (2004) The role of reactive oxygen species and apoptosis in the pathogenesis of varicocele in a rat model and efficiency of vitamin E treatment. Int J Androl 27:228–233CrossRefPubMed Cam K, Simsek F, Yuksel M et al (2004) The role of reactive oxygen species and apoptosis in the pathogenesis of varicocele in a rat model and efficiency of vitamin E treatment. Int J Androl 27:228–233CrossRefPubMed
21.
22.
go back to reference Izu H, Inouye S, Fujimoto M et al (2004) Heat shock transcription factor 1 is involved in quality-control mechanisms in male germ cells. Biol Reprod 70:18–24CrossRefPubMed Izu H, Inouye S, Fujimoto M et al (2004) Heat shock transcription factor 1 is involved in quality-control mechanisms in male germ cells. Biol Reprod 70:18–24CrossRefPubMed
23.
go back to reference Lue YH, Hikim AP, Swerdloff RS et al (1999) Single exposure to heat induces stage-specific germ cell apoptosis in rats: role of intratesticular testosterone on stage specificity. Endocrinology 140:1709–1717CrossRefPubMed Lue YH, Hikim AP, Swerdloff RS et al (1999) Single exposure to heat induces stage-specific germ cell apoptosis in rats: role of intratesticular testosterone on stage specificity. Endocrinology 140:1709–1717CrossRefPubMed
24.
go back to reference Hassan A, El-Nashar EM, Mostafa T (2009) Programmed cell death in varicocele-bearing testes. Andrologia 41:39–45CrossRefPubMed Hassan A, El-Nashar EM, Mostafa T (2009) Programmed cell death in varicocele-bearing testes. Andrologia 41:39–45CrossRefPubMed
25.
go back to reference Yin Y, DeWolf WC, Morgentaler A (1998) Experimental cryptorchidism induces testicular germ cell apoptosis by p53-dependent and -independent pathways in mice. Biol Reprod 58:492–496CrossRefPubMed Yin Y, DeWolf WC, Morgentaler A (1998) Experimental cryptorchidism induces testicular germ cell apoptosis by p53-dependent and -independent pathways in mice. Biol Reprod 58:492–496CrossRefPubMed
26.
go back to reference Morgentaler A, Stahl BC, Yin Y (1999) Testis and temperature: an historical, clinical, and research perspective. J Androl 20:189–195PubMed Morgentaler A, Stahl BC, Yin Y (1999) Testis and temperature: an historical, clinical, and research perspective. J Androl 20:189–195PubMed
27.
go back to reference Lenzi A, Culasso F, Gandini L et al (1993) Placebo-controlled, double-blind, cross-over trial of glutathione therapy in male infertility. Hum Reprod 8:1657–1662PubMed Lenzi A, Culasso F, Gandini L et al (1993) Placebo-controlled, double-blind, cross-over trial of glutathione therapy in male infertility. Hum Reprod 8:1657–1662PubMed
28.
go back to reference Kessopoulou E, Powers HJ, Sharma KK et al (1995) A double-blind randomized placebo cross-over controlled trial using the antioxidant vitamin E to treat reactive oxygen species associated male infertility. Fertil Steril 64:825–831PubMed Kessopoulou E, Powers HJ, Sharma KK et al (1995) A double-blind randomized placebo cross-over controlled trial using the antioxidant vitamin E to treat reactive oxygen species associated male infertility. Fertil Steril 64:825–831PubMed
Metadata
Title
Elevated scrotal temperature, but not varicocele grade, reflects testicular oxidative stress-mediated apoptosis
Authors
Koji Shiraishi
Hiroshi Takihara
Hideyasu Matsuyama
Publication date
01-06-2010
Publisher
Springer-Verlag
Published in
World Journal of Urology / Issue 3/2010
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-009-0462-5

Other articles of this Issue 3/2010

World Journal of Urology 3/2010 Go to the issue