Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Induction and Determination of Apoptotic and Necrotic Cell Death by Cadmium Chloride in Testis Tissue of Mouse

Authors
Department of Anatomy, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Abstract
Background: Cadmium chloride which is potentially toxic is currently used in industry. The toxic effects of cadmium on testes have been reported to range from apoptosis to necrosis, with different effects on fertility. This research aimed to study the effect of different doses of cadmium on testicular tissues at acute stage by light and electron microscopy. Methods: Cadmium chloride was injected into mature Balb/c mice intraperitoneally in 7 doses. Five mice were studied in each group. After 48 hr, the testes were extracted and prepared for light microscopy. Then two concentrations (15 and 25 µM/kg) of them were selected for electron microscopic study based on histological changes. The cellular changes of luminal epithelium of seminiferous tubules were studied under an electron microscope. Histological and ultrastructural changes were reported. Results: The absence of sperm in the tubules was observed at 20 µM/kg concentration. At 25 µM/kg, histological destruction and epithelial damages were observed. Histological changes were not remarkable at 5 and 10 µM/kg. However, ultrastructural changes of seminiferous tubules at 20 µM/kg included spermatogonial cell death. At 25 µM/kg, vacuolation of Sertoli cells and death of spermatids as well as spermatocytes were observed. Cell death in the tubules was limited to germ cells. However, Sertoli cells exhibited architectural alterations without any cell death. Conclusion: Both apoptosis and necrosis occurred in testicular tissue by exposure to cadmium in a concentration-dependent manner. Gonadal cells were sensitive to cadmium administration. Supportive cells such as Sertoli cells in seminiferous tubules did not exhibit sensitivity to cadmium.
Keywords

  1. Thompson J, Bannigan J. Cadmium: toxic effects on the reproductive system and the embryo. Reprod Toxicol. 2008;25(3):304-15.
  2. Hayes RB. The carcinogenicity of metals in humans. Cancer Causes Control. 1997;8(3):371-85.
  3. Tomatis L. The IARC program on the evaluation of the carcinogenic risk of chemicals to man. Ann N Y Acad Sci. 1976;271:396-409.
  4. Blanco A, Moyano R, Vivo J, Flores-Acuna R, Molina A, Blanco C, et al. Quantitative changes in the testicular structure in mice exposed to low doses of cadmium. Environ Toxicol Pharmacol. 2007;23(1):96-101.
  5. El-Shahat AE, Gabr A, Meki A, Mehana E. Altered testicular morphology and oxidative stress induced by cadmium in experimental rats and protective effect of simultaneous green tea extract. Int J Morphol. 2009;27:757-64.
  6. Santos FW, Oro T, Zeni G, Rocha JB, do Nascimento PC, Nogueira CW. Cadmium induced testicular damage and its response to administration of succimer and diphenyl diselenide in mice. Toxicol Lett. 2004;152(3):255-63.
  7. Patra RC, Rautray AK, Swarup D. Oxidative stress in lead and cadmium toxicity and its amelioration. Vet Med Int. 2011;2011:457327.
  8. Hikim APS, YueJia YHL, Wang C, Swerdloff RS, editors. Apoptotic signaling in male germ cells. New York: Cambridge University Press; 2011. 283 p. (Green DR, Reed JC, editors. Apoptosis: physiology and Pathology; vol. 25).
  9. Angenard G, Muczynski V, Coffigny H, Pairault C, Duquenne C, Frydman R, et al. Cadmium increases human fetal germ cell apoptosis. Environ Health Perspect. 2010;118(3):331-7.
  10. Sharma S, Kaur S. Histopathological effects of acute and chronic doses of cadmium on testes of albino mice. J Exp Zool India. 2012;15(1):107-11.
  11. Zhou T, Jia X, Chapin RE, Maronpot RR, Harris MW, Liu J, et al. Cadmium at a non-toxic dose alters gene expression in mouse testes. Toxicol Lett. 2004;154(3):191-200.
  12. Siu ER, Mruk DD, Porto CS, Cheng CY. Cadmium-induced testicular injury. Toxicol Appl Pharmacol. 2009;238(3):240-9.
  13. Wong CH, Mruk DD, Lui WY, Cheng CY. Regulation of blood-testis barrier dynamics: an in vivo study. J Cell Sci. 2004;117(Pt 5):783-98.
  14. Xu C, Johnson JE, Singh PK, Jones MM, Yan H, Carter CE. In vivo studies of cadmium-induced apoptosis in testicular tissue of the rat and its modulation by a chelating agent. Toxicology. 1996;107(1):1-8.
  15. Ogawa Y, Itoh M, Hirai S, Suna S, Naito M, Qu N, et al. Cadmium exposure increases susceptibility to testicular autoimmunity in mice. J Appl Toxicol. 2013;33(7):652-60.
  16. Waalkes MP, Anver M, Diwan BA. Carcinogenic effects of cadmium in the noble (NBL/Cr) rat: induction of pituitary, testicular, and injection site tumors and intraepithelial proliferative lesions of the dorsolateral prostate. Toxicol Sci. 1999;52(2):154-61.
  17. Hew KW, Ericson WA, Welsh MJ. A single low cadmium dose causes failure of spermiation in the rat. Toxicol Appl Pharmacol. 1993;121(1):15-21.
  18. Ji YL, Wang H, Zhao XF, Wang Q, Zhang C, Zhang Y, et al. Crosstalk between endoplasmic reticulum stress and mitochondrial pathway mediates cadmium-induced germ cell apoptosis in testes. Toxicol Sci. 2011;124(2):446-59.
  19. Kim J, Soh J. Cadmium-induced apoptosis is mediated by the translocation of AIF to the nucleus in rat testes. Toxicol Lett. 2009;188(1):45-51.
  20. Siu ER, Wong EW, Mruk DD, Sze KL, Porto CS, Cheng CY. An occludin-focal adhesion kinase protein complex at the blood-testis barrier: a study using the cadmium model. Endocrinology. 2009;150(7):3336-44.
  21. Obianime AW, Roberts II. Antioxidants, cadmium-induced toxicity, serum biochemical and the histological abnormalities of the kidney and testes of the male Wistar rats. Niger J Physiol Sci. 2009;24(2):177-85.
  22. Ognjanovic BI, Markovic SD, Ethordevic NZ, Trbojevic IS, Stajn AS, Saicic ZS. Cadmium-induced lipid peroxidation and changes in antioxidant defense system in the rat testes: protective role of coenzyme Q(10) and vitamin E. Reprod Toxicol. 2010;29(2):191-7.
  23. Oliveira H, Lopes T, Almeida T, Pereira Mde L, Santos C. Cadmium-induced genetic instability in mice testis. Hum Exp Toxicol. 2012;31(12):1228-36.
  24. Akinloye O, Arowojolu AO, Shittu OB, Anetor JI. Cadmium toxicity: a possible cause of male infertility in Nigeria. Reprod Biol. 2006;6(1):17-30.