Exercise and Supraphysiological Dose of Nandrolone Deconoate Increase Apoptosis in Spermatogenic Cells
Saeed Shokri
Anatomy Department, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
Search for more papers by this authorRobert John Aitken
Discipline of Biological Sciences, ARC Centre of Excellence in Biotechnology and Development, University of Newcastle, Newcastle, NSW, Australia
Search for more papers by this authorMirabbas Abdolvahhabi
Anatomy Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorFarid Abolhasani
Anatomy Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorFahimeh Mohammad Ghasemi
Anatomy Department, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
Search for more papers by this authorIraj Kashani
Anatomy Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorShahram Ejtemaeimehr
Pharmacology Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorShahin Ahmadian
Electron Microscopic Department, Institute of biophysics and biochemistry, University of Tehran, Tehran, Iran
Search for more papers by this authorBagher Minaei
Anatomy Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorMohammad Ali Naraghi
Anatomy Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorMohammad Barbarestani
Anatomy Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorSaeed Shokri
Anatomy Department, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
Search for more papers by this authorRobert John Aitken
Discipline of Biological Sciences, ARC Centre of Excellence in Biotechnology and Development, University of Newcastle, Newcastle, NSW, Australia
Search for more papers by this authorMirabbas Abdolvahhabi
Anatomy Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorFarid Abolhasani
Anatomy Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorFahimeh Mohammad Ghasemi
Anatomy Department, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
Search for more papers by this authorIraj Kashani
Anatomy Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorShahram Ejtemaeimehr
Pharmacology Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorShahin Ahmadian
Electron Microscopic Department, Institute of biophysics and biochemistry, University of Tehran, Tehran, Iran
Search for more papers by this authorBagher Minaei
Anatomy Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorMohammad Ali Naraghi
Anatomy Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorMohammad Barbarestani
Anatomy Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Search for more papers by this authorAbstract
Abstract: Anabolic-androgenic steroids are used at high doses by athletes for improving athletic ability, physical appearance and muscle mass. Unfortunately, the abuse of these agents has significantly increased. It has been established that exercise and high doses of anabolic-androgenic steroids may influence the hypothalamic-pituitary-gonadal axis, which can in turn affect testicular apoptosis. However, the effect of the combination of exercise and high dose of anabolic-androgenic steroids on testicular apoptosis is not known. We investigated the combined effects of exercise and high doses of nandrolone decanoate on apoptosis in the spermatogenic cell lineage. Five groups of male Wistar strain albino rats were treated as follows for 8 weeks: solvent of nandrolone decanoate (peanut oil) as a vehicle (Sham); nandrolone decanoate (10 mg/kg/weekly) (nandrolone decanoate); exercise (1 hr/day, 5 days a week) (exercise); nandrolone decanoate (10 mg/kg/weekly) and exercise (1 hr/day, 5 days a week) (nandrolone decanoate exercise); and sedentary control without any injection or exercise (Control). Apoptosis in the male germ line was characterized by TUNEL, caspase-3 assay and transmission electron microscopy. The weights of the testis and accessory sex organs, as well as sperm parameters significantly decreased in the experimental groups relative to the sham and control groups (p ≤ 0.05). Germ cell apoptosis and a significant decrease in the number of germ cell layers in nandrolone decanoate exercise-treated testes were observed (p ≤ 0.05). Exercise training seems to increase the extent of apoptotic changes caused by supraphysiological dose of nandrolone decanoate in rats, which in turn affects fertility.
References
- 1 Wood RI. Reinforcing aspects of androgens. Physiol Behav 2004; 83: 279–89.
- 2 Clark AS, Harrold EV, Fast AS. Anabolic-androgenic steroid effects on the sexual behavior of intact male rats. Horm Behav 1997; 31: 35–46.
- 3 Feinberg MJ, Lumia AR, McGinnis MY. The effect of anabolic-androgenic steroids on sexual behavior and reproductive tissues in male rats. Physiol Behav 1997; 62: 23–30.
- 4 Graham MR, Davies B, Grace FM, Kicman A, Baker JS. Anabolic steroid use: patterns of use and detection of doping. Sports Med 2008; 38: 505–25.
- 5 Lucia A, Chicharro JL, Perez M, Serratosa L, Bandres F, Legido JC. Reproductive function in male endurance athletes: sperm analysis and hormonal profile. J Appl Physiol 1996; 81: 2627–36.
- 6 Giampietri C, Petrungaro S, Coluccia P, D’Alessio A, Starace D, Riccioli A et al. Germ cell apoptosis control during spermatogenesis. Contraception 2005; 72: 298–302.
- 7 Orth JM, Gunsalus GL, Lamperti AA. Evidence from Sertoli cell-depleted rats indicates that spermatid number in adults depends on numbers of Sertoli cells produced during perinatal development. Endocrinology 1988; 122: 787–94.
- 8 Clerico A, Ferdeghini M, Palombo C, Leoncini R, Del Chicca MG, Sardano G et al. Effect of anabolic treatment on the serum levels of gonadotropins, testosterone, prolactin, thyroid hormones and myoglobin of male athletes under physical training. J Nucl Med Allied Sci 1981; 25: 79–88.
- 9 Kolasa A, Marchlewicz M, Wenda-Rozewicka L, Wiszniewska B. Morphology of the testis and the epididymis in rats with dihydrotestosterone (DHT) deficiency. Rocz Akad Med Bialymst 2004; 49(Suppl. 1): 117–9.
- 10 Lumia AR. The relationships among testosterone, conditioned aggression, and dominance in male pigeons. Horm Behav 1972; 3: 277–86.
- 11 Schurmeyer T, Knuth UA, Belkien L, Nieschlag E. Reversible azoospermia induced by the anabolic steroid 19-nortestosterone. Lancet 1984; 1: 417–20.
- 12 Sugizaki MM, Dal Pai-Silva M, Carvalho RF, Padovani CR, Bruno A, Nascimento AF et al. Exercise training increases myocardial inotropic response in food restricted rats. Int J Cardiol 2006; 112: 191–201.
- 13 Portes LA, Tucci PJ. Swim training attenuates myocardial remodeling and the pulmonary congestion in Wistar rats with secondary heart failure to myocardial infarction. Arq Bras Cardiol 2006; 87: 54–9.
- 14 Gunduz F, Senturk UK, Kuru O, Aktekin B, Aktekin MR. The effect of one year’s swimming exercise on oxidant stress and antioxidant capacity in aged rats. Physiol Res 2004; 53: 171–6.
- 15 World Health Organization (WHO). WHO Manual for the Examination of Human Semen and Sperm–Cervical Mucus Interaction, 4th edn. Cambridge University Press, Cambridge, 1999.
- 16 Wyrobek AJ, Gordon LA, Burkhart JG, Francis MW, Kapp RW Jr, Letz G et al. An evaluation of the mouse sperm morphology test and other sperm tests in nonhuman mammals. A report of the U.S. Environmental Protection Agency Gene-Tox Program. Mutat Res 1983; 115: 1–72.
- 17 Miller DC, Peron SE, Keck RW, Kropp KA. Effects of hypothermia on testicular ischemia. J Urol 1990; 143: 1046–8.
- 18 Johnsen SG. Testicular biopsy score count – a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormones 1970; 1: 2–25.
- 19 McIntyre KL, Porter DM, Henderson LP. Anabolic androgenic steroids induce age-, sex-, and dose-dependent changes in GABA(A) receptor subunit mRNAs in the mouse forebrain. Neuropharmacology 2002; 43: 634–45.
- 20 O’Sullivan AJ, Kennedy MC, Casey JH, Day RO, Corrigan B, Wodak AD. Anabolic-androgenic steroids: medical assessment of present, past and potential users. Med J Aust 2000; 173: 323–7.
- 21 Torres-Calleja J, Gonzalez-Unzaga M, Celis-Carrillo R, Calzada-Sanchez L, Pedron N. Effect of androgenic anabolic steroids on sperm quality and serum hormone levels in adult male bodybuilders. Life Sci 2001; 68: 1769–74.
- 22 Ludwig DJ. The effect of androgen on spermatogenesis. Endocrinology 1950; 46: 453–81.
- 23 Hackney AC. Endurance exercise training and reproductive endocrine dysfunction in men: alterations in the hypothalamic-pituitary-testicular axis. Curr Pharm Des 2001; 7: 261–73.
- 24 Trasler JM, Hales BF, Robaire B. Chronic low dose cyclophosphamide treatment of adult male rats: effect on fertility, pregnancy outcome and progeny. Biol Reprod 1986; 34: 275–83.
- 25 Karila T, Hovatta O, Seppala T. Concomitant abuse of anabolic androgenic steroids and human chorionic gonadotrophin impairs spermatogenesis in power athletes. Int J Sports Med 2004; 25: 257–63.
- 26 Arce JC, De Souza MJ. Exercise and male factor infertility. Sports Med 1993; 15: 146–69.
- 27 Hackney AC. The male reproductive system and endurance exercise. Med Sci Sports Exerc 1996; 28: 180–9.
- 28 Davies KJ, Quintanilha AT, Brooks GA, Packer L. Free radicals and tissue damage produced by exercise. Biochem Biophys Res Commun 1982; 107: 1198–205.
- 29 Ji LL. Exercise and oxidative stress: role of the cellular antioxidant systems. Exerc Sport Sci Rev 1995; 23: 135–66.
- 30 Kanter M. Free radicals and exercise: effects of nutritional antioxidant supplementation. Exerc Sport Sci Rev 1995; 23: 375–97.
- 31 Leaf DA, Kleinman MT, Hamilton M, Barstow TJ. The effect of exercise intensity on lipid peroxidation. Med Sci Sports Exerc 1997; 29: 1036–9.
- 32 Sjodin B, Hellsten WY, Apple FS. Biochemical mechanisms for oxygen free radical formation during exercise. Sports Med 1990; 10: 236–54.
- 33 Pey A, Saborido A, Blazquez I, Delgado J, Megias A. Effects of prolonged stanozolol treatment on antioxidant enzyme activities, oxidative stress markers, and heat shock protein HSP72 levels in rat liver. J Steroid Biochem Mol Biol 2003; 87: 269–77.
- 34 Chaves EA, Pereira-Junior PP, Fortunato RS, Masuda MO, De Carvalho AC, De Carvalho DP et al. Nandrolone decanoate impairs exercise-induced cardioprotection: role of antioxidant enzymes. J Steroid Biochem Mol Biol 2006; 99: 223–30.
- 35
Husain K,
Somani SM.
Interaction of exercise training and chronic ethanol ingestion on testicular antioxidant system in rat.
J Appl Toxicol
1998; 18: 421–9.
10.1002/(SICI)1099-1263(199811/12)18:6<421::AID-JAT532>3.0.CO;2-R CAS PubMed Web of Science® Google Scholar
- 36 Tesarik J, Greco E, Cohen-Bacrie P, Mendoza C. Germ cell apoptosis in men with complete and incomplete spermiogenesis failure. Mol Hum Reprod 1998; 4: 757–62.
- 37 Agarwal A, Said TM. Oxidative stress, DNA damage and apoptosis in male infertility: a clinical approach. BJU Int 2005; 95: 503–7.
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