Effects of Lithium on Levels of Testosterone, Pituitary Gonadotropins, and Testis Tissue in Adult Male Rats

Document Type : Original Article (s)

Authors

1 Young Researchers and Elites club, Science and Research Branch, Islamic Azad University, Tehran, Iran

2 Assistant Professor, Department of Anatomical Sciences, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

3 Department of Biology- Biochemistry, Islamic Azad University, Science and Research Branch, Tehran, Iran

4 General Practitioner, Mahneshan Health Office, Zanjan University of Medical Sciences, Zanjan, Iran

5 Assistant Professor, Department of Community Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

6 Deputy of Research, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Lithium is used to treat bipolar disorder. Considering the importance of sex cells in reproduction and transmission of hereditary traits, in this study, the effects of lithium were investigated onto the level of testosterone, gonadotropins, testis tissue, and spermatogenesis.Methods: An experimental study was performed on 16 rats in two groups. The experimental group was intraperitoneally injected with 180 mg/kg/body weight of lithium carbonate solution for 40 days. The control group did not receive any medicine. The testes were removed, fixed in 10% formalin, and stained with hematoxylin-eosin. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were measured by radioimmunoassay and the collected data was analyzed.Findings: LH, FSH, and testosterone levels were significantly lower in the experimental group than in the control group (P < 0.001). Weight and length of the testes and weight of epididymis showed significant reductions in the experimental group compared to the controls. Significantly fewer spermatogonia, primary spermatocytes, and spermatid were seen in the experimental group than in the control group (P < 0.001). However, the two groups were not significantly different in terms of testis width or the number of Sertoli cells.Conclusion: Lithium must be cautiously prescribed by considering each patient’s test results, dose of drug, and duration of use.

Keywords

References

  1. Odagaki Y, Koyama T, Matsubara S, Yamashita I. Effects of lithium on the beta-adrenergic receptor-adenylate cyclase system in rat cerebral cortical membranes. Jpn J Pharmacol 1991; 55(4): 407-14.
  2. Alda M. Pharmacogenetics of lithium response in bipolar disorder. J Psychiatry Neurosci 1999; 24(2): 154-8.
  3. Hill EJ, Woehrling EK, Prince M, Coleman MD. Differentiating human NT2/D1 neurospheres as a versatile in vitro 3D model system for developmental neurotoxicity testing. Toxicology 2008; 249(2-3): 243-50.
  4. Zarnescu O, Zamfirescu G. Effects of lithium carbonate on rat seminiferous tubules: an ultrastructural study. Int J Androl 2006; 29(6): 576-82.
  5. Nokhbatolfoghahai M, Parivar K. Teratogenic effect of lithium carbonate in early development of BALB/c mouse. Anat Rec (Hoboken ) 2008; 291(9): 1088-96.
  6. Ghosh PK, Biswas NM, Ghosh D. Effect of lithium chloride on testicular steroidogenesis and gametogenesis in immature male rats. Acta Endocrinol (Copenh) 1991; 124(1): 76-82.
  7. Grinspon RP, Rey RA. Anti-mullerian hormone and sertoli cell function in paediatric male hypogonadism. Horm Res Paediatr 2010; 73(2): 81-92.
  8. Shittu Lukeman AJ, Shittu Remilekun K, Osinubi Abraham AA, Tayo Adetokunbo A. Mesterolone (Proviron) induces low sperm quality with reduction in sex hormone profile in adult male Sprague Dawley rats testis. Sci. Res. Essay 2009; 4(4): 320-7.
  9. Carreau S, Bouraima-Lelong H, Delalande C. Estrogen, a female hormone involved in spermatogenesis. Adv Med Sci 2012; 57(1): 31-6.
  10. Carreau S, Silandre D, Bois C, Bouraima H, Galeraud-Denis I, Delalande C. Estrogens: a new player in spermatogenesis. Folia Histochem Cytobiol 2007; 45(Suppl 1): S5-10.
  11. Zargham M. Endocrine and metabolism. Tehran, Iran: Baraye Farda Publications; 2002. p. 119-20. [In Persian].
  12. Skakkebaek NE. Testicular dysgenesis syndrome: new epidemiological evidence. Int J Androl 2004; 27(4): 189-91.
  13. Toppari J, Larsen JC, Christiansen P, Giwercman A, Grandjean P, Guillette LJ, Jr., et al. Male reproductive health and environmental xenoestrogens. Environ Health Perspect 1996; 104(Suppl 4): 741-803.
  14. Schloesser RJ, Martinowich K, Manji HK. Mood-stabilizing drugs: mechanisms of action. Trends Neurosci 2012; 35(1): 36-46.
  15. Allagui MS, Hfaiedh N, Croute F, Guermazi F, Vincent C, Soleilhavoup JP, et al. Side effects of low serum lithium concentrations on renal, thyroid, and sexual functions in male and female rats. C R Biol 2005; 328(10-11): 900-11. [In French].
  16. Ghosh D, Biswas NM, Ghosh PK. Studies on the effect of prolactin treatment on testicular steroidogenesis and gametogenesis in lithium-treated rats. Acta Endocrinol (Copenh) 1991; 125(3): 313-8.
  17. Banerji TK, Maitra SK, Basu A, Hawkins HK. Lithium-induced alterations in the testis of the male roseringed parakeet (Psittacula krameri) : evidence for significant structural changes and disruption in the spermatogenetic activity. Endocr Res 1999; 25(1): 35-49.
  18. Al-Azemi M, Omu FE, Kehinde EO, Anim JT, Oriowo MA, Omu AE. Lithium protects against toxic effects of cadmium in the rat testes. J Assist Reprod Genet 2010; 27(8): 469-76.
  19. Wong RW, Kwan RW, Mak PH, Mak KK, Sham MH, Chan SY. Overexpression of epidermal growth factor induced hypospermatogenesis in transgenic mice. J Biol Chem 2000; 275(24): 18297-301.
  20. Uguralp S, Bay KA, Mizrak B, Kaymaz F, Kiziltay A, Hasirci N. The effect of sustained and local administration of epidermal growth factor on improving bilateral testicular tissue after torsion. Urol Res 2004; 32(5): 323-31.
  21. Haneji T, Koide SS, Tajima Y, Nishimune Y. Differential effects of epidermal growth factor on the differentiation of type A spermatogonia in adult mouse cryptorchid testes in vitro. J Endocrinol 1991; 128(3): 383-8.
  22. Ito R, Abe SI. FSH-initiated differentiation of newt spermatogonia to primary spermatocytes in germ-somatic cell reaggregates cultured within a collagen matrix. Int J Dev Biol 1999; 43(2): 111-6.
  23. Wahab-Wahlgren A, Martinelle N, Holst M, Jahnukainen K, Parvinen M, Soder O. EGF stimulates rat spermatogonial DNA synthesis in seminiferous tubule segments in vitro. Mol Cell Endocrinol 2003; 201(1-2): 39-46.
  24. Toghiani Sh, Gholami M, Zendedel A, Assadollahi V. The effects of low-dose lithium carbonate on the spermatogenic parameter in the adults male wistar rats. Life Science Journal 2012; 9(4): 4360-7.
  25. Allagui MS, Hfaiedh N, Vincent C, Guermazi F, Murat JC, Croute F, et al. Changes in growth rate and thyroid- and sex-hormones blood levels in rats under sub-chronic lithium treatment. Hum Exp Toxicol 2006; 25(5): 243-50.
  26. Thakur SC, Thakur SS, Chaube SK, Singh SP. Subchronic supplementation of lithium carbonate induces reproductive system toxicity in male rat. Reprod Toxicol 2003; 17(6): 683-90.
  27. Mathur N, Pandey G, Jain GC. Male reproductive toxicity of some selected metals: A review. J Biol Sci 2010; 10(5): 396-404.
  28. Ali A, Kttaann A, Alqudisi F, Karim S. Ultrastructural changes of the testicular tissues of immature and mature mice under the effect of lithium carbonate. Bull Alex Fac Med 2008; 44(3): 805-15.
Journal of Isfahan Medical School
Volume 31, Issue 227 - Serial Number 227
January and February 2013
Pages 191-199

Files

History

  • Receive Date: 27 January 2013
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics