Skip to main content
SpringerLink
Log in

Carbon disulfide induces mitochondria-mediated apoptosis in Sertoli-germ cells coculture

  • Original Paper
  • Published:
Molecular & Cellular Toxicology Aims and scope Submit manuscript

An Erratum to this article was published on 01 September 2015

Abstract

Carbon disulfide (CS2), a common organic solvent, induces a variety of adverse effects in the male reproductive system. In this study, we investigated the cytotoxicity, ultrastructural changes, and potential apoptotic induction mechanisms of CS2 in mixed cultures of Sertoli and germ cells. Sertoli and germ cells were cocultured and treated with CS2 for 24 h. Growth rates were noted, and apoptotic cells were identified by Hoechst 33258 staining. Ultrastructure changes were observed via transmission electron microscopy (TEM). Mitochondrial membrane potential and expressions of apoptosis-related factors (cytochrome c, Bax, Bcl-2, caspase-3 and caspase-9) were examined by JC-1 staining, western blot, and real-time PCR. The results showed that CS2 treatment was associated with reduced growth rates of Sertoli-germ cells. Ultrastructure changes in Sertoli-germ cells treated with CS2 were typical of apoptosis. In addition, CS2 treatment depolarized mitochondrial membrane potential, upregulated Bax levels and downregulated Bcl-2 levels, released cytochrome c from the mitochondrial intermembrane space to the cytosol, and triggered mitochondria-mediated apoptosis. Subsequently, caspase-9 and caspase-3 were activated, resulting in Sertoli-germ cells apoptosis. The above data suggest that CS2 has adverse effect on the viability of Sertoli-germ cells and induces apoptosis through mitochondrial pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Sills, R. C., Valentine, W. M., Moser, V., Graham, D. G. & Morgan, D. L. Characterization of carbon dis ulfide neurotoxicity in C57BL6 mice: behavioral, morpholog-ic, and molecular effects. Toxicol Pathol 28:142 (2000).

    Google Scholar 

  2. Chuang, W. L. et al. Carbon disulfide encephalopa-thy: cerebral microangiopathy. Neurotoxicology 28: 387 (2007).

    Google Scholar 

  3. Tan, X. et al. Carbon disulfide cytotoxicity on cultured cardiac myocyte cell of rats. Ecotoxicol Environ Saf 55: 168 (2003).

    Google Scholar 

  4. Tan, X. et al. Cross-sectional study of cardiovascular effects of carbon disulfide among Chinese workers of a viscose factory. Int J Hyg Environ Health 207:217 (2004).

    Google Scholar 

  5. Zenick, H., Blackburn, K., Hope, E. & Baldwin, D. An evaluation of the copulatory, endocrinologic, and sper-matotoxic effects of carbon disulfide in the rat. Toxicol Appl Pharmacol 73:275 (1984).

    Google Scholar 

  6. Tepe, S. J. & Zenick, H. The effects of carbon disulfide on the reproductive system of the male rat. Toxicology 32:47 (1984).

    Google Scholar 

  7. Vanhoorne, M., Comhaire, F. & De Bacquer, D. Epide-miological study of the effects of carbon disulfide on male sexuality and reproduction. Arch Environ Health 49:273 (1994).

    Google Scholar 

  8. Patel, K. G., Yadav, P. C., Pandya, C. B. & Saiyed, H. N. Male exposure mediated adverse reproductive out-comes in carbon disulphide exposed rayon workers. J Environ Biol 25:413 (2004).

    Google Scholar 

  9. Ma, J. Y. et al. The effects of carbon disulfide on male sexual function and semen quality. Toxicol Ind Health 26:375 (2010).

    Google Scholar 

  10. Huang, X. et al. Nitric oxide mediated effects on re-productive toxicity caused by carbon disulfide in male rats. Environ Toxicol Pharmacol 34:679 (2012).

    Google Scholar 

  11. Mihalache, C. & Mihalache, G. Histologic aspects of the testis in experimental carbon disulfide poisoning. Rev Med Chir Soc Med Nat Iasi 93:339 (1989).

    Google Scholar 

  12. Koji, T. & Hishikawa, Y. Germ cell apoptosis and its molecular trigger in mouse testes. Arch Histol Cytol 66:1 (2003).

    Google Scholar 

  13. Shukla, K. K., Mahdi, A. A. & Rajender, S. Apopto-sis, spermatogenesis and male infertility. Front Bios-ci (Elite Ed) 4:746 (2012).

    Google Scholar 

  14. Guo, Y. et al. Carbon disulfide induces rat testicular injury via mitochondrial apoptotic pathway. Chemo-sphere 108:367 (2014).

    Google Scholar 

  15. Gao, Y., Mruk, D. D. & Cheng, C. Y. Sertoli cells are the target of environmental toxicants in the testis-a mechanistic and therapeutic insight. Expert Opin Ther Targets 1 (2015).

  16. Griswold, M. D. The central role of Sertoli cells in spermatogenesis. Semin Cell Dev Biol 9:411 (1998).

    Article  CAS  PubMed  Google Scholar 

  17. Lee, J., Richburg, J. H., Younkin, S. C. & Boekelheide, K. The Fas system is a key regulator of germ cell apop-tosis in the testis. Endocrinology 138:2081 (1997).

    Google Scholar 

  18. Aslam, I. & Fishel, S. Short-term in-vitro culture and cryopreservation of spermatogenic cells used for hu-man in-vitro conception. Hum Reprod 13:634 (1998).

    Google Scholar 

  19. Hue, D. et al. Meiotic differentiation of germinal cells in three-week cultures of whole cell population from rat seminiferous tubules. Biol Reprod 59:379 (1998).

    Google Scholar 

  20. Pepllonska, B., Sobala, W. & Szeszenia-Dabrowska, N. Mortality pattern in the cohort of workers exposed to carbon disulfide. Int J Occup Med Environ Health 14: 267 (2001).

    Google Scholar 

  21. Vanhoorne, M., Comhaire, F. & De Bacquer, D. Epide-miological study of the effects of carbon disulfide on male sexuality and reproduction. Arch Environ Health 49:273 (1994).

    Google Scholar 

  22. Patel, K. G., Yadav, P. C., Pandya, C. B. & Saiyed, H. N. Male exposure mediated adverse reproductive out-comes in carbon disulphide exposed rayon workers. J Environ Biol 25:413 (2004).

    Google Scholar 

  23. Ma, J. Y. et al. The effects of carbon disulfide on male sexual function and semen quality. Toxicol Ind Health 26:375 (2010).

    Google Scholar 

  24. Tepe, S. J. & Zenick, H. The effects of carbon disulfide on the reproductive system of the male rat. Toxicology 32:47 (1984).

    Google Scholar 

  25. Kumar, S. et al. Detection of germ cell genotoxic po-tential of carbon disulphide using sperm head shape abnormality test. Hum Exp Toxicol 18:731 (1999).

    Google Scholar 

  26. Huang, X. et al. Nitric oxide mediated effects on re-productive toxicity caused by carbon disulfide in male rats. Environ Toxicol Pharmacol 34:679 (2012).

    Google Scholar 

  27. Vaux, D. L. & Korsmeyer, S. J. Cell death in develop-ment. Cell 96:245 (1999).

    Google Scholar 

  28. Hikim, A. P. et al. Spontaneous germ cell apoptosis in humans: evidence for ethnic differences in the suscep-tibility of germ cells to programmed cell death. J Clin Endocrinol Metab 83:152 (1998).

    Google Scholar 

  29. Norbury, C. J. & Hickson, I. D. Cellular responses to DNA damage. Annu Rev Pharmacol Toxicol 41:367 (2001).

    Google Scholar 

  30. Guo, Y. et al. Carbon disulfide induces rat testicular injury via mitochondrial apoptotic pathway. Chemo-sphere 108:367 (2014).

    Google Scholar 

  31. Zhang, B. et al. DNA damage and apoptosis of endo-metrial cells cause loss of the early embryo in mice exposed to carbon disulfide. Toxicol Appl Pharmacol 273:381 (2013).

    Google Scholar 

  32. Brenner, D. & Mak, T. W. Mitochondrial cell death effectors. Curr Opin Cell Biol 21:871 (2009).

    Google Scholar 

  33. Danial, N. N. & Korsmeyer, S. J. Cell death: critical control points. Cell 116:205 (2004).

    Google Scholar 

  34. Kluck, R. M., Bossy-Wetzel, E., Green, D. R. and New-meyer, D. D. The release of cytochrome c from mito-chondria: a primary site for Bcl-2 regulation of apopto-sis. Science 275:1132 (1997).

    Google Scholar 

  35. Wei, M. C. et al. Proapoptotic BAX and BAK: a req-uisite gateway to mitochondrial dysfunction and death. Science 292:727 (2001).

    Google Scholar 

  36. Suen, D. F., Norris, K. L. & Youle, R. J. Mitochondrial dynamics and apoptosis. Genes Dev 22:1577 (2008).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Oltvai, Z. N., Milliman, C. L. & Korsmeyer, S. J. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74: 609 (1993).

    Article  CAS  PubMed  Google Scholar 

  38. Thornberry, N. A. & Lazebnik, Y. Caspases: enemies within. Science 281:1312 (1998).

    Article  CAS  PubMed  Google Scholar 

  39. Pradelli, L. A., Beneteau, M. & Ricci, J. E. Mitochon-drial control of caspase-dependent and-independent cell death. Cell Mol Life Sci 67:1589 (2010).

    Article  CAS  PubMed  Google Scholar 

  40. Porter, A. G. & Janicke, R. U. Emerging roles of caspase-3 in apoptosis. Cell Death Differ 6:99 (1999).

    Article  CAS  PubMed  Google Scholar 

  41. Adhikari, N., Sinha, N. & Saxena, D. K. Effect of lead on Sertoli-germ cell coculture of rat. Toxicol Lett 116: 45 (2000).

    Article  CAS  PubMed  Google Scholar 

  42. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55 (1983).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Key Lab of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China

    Wei Wang, Zhen Zhang, Yinsheng Guo, Yu Dong, Xiaoyu Huang & Guoyuan Chen

  2. Department of Quality Control, Jiangxi Cancer Hospital, Nanchang, 330029, China

    Wei Wang

  3. Pudong New Area Center for Disease Control and Prevention, 3039 Zhang Yang Road, Shanghai, 200136, China

    Zhen Zhang

  4. Department of Environmental Health, School of Public Health, Shanghai Jiaotong University, Shanghai, 200025, China

    Yijun Zhou

Authors
  1. Wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhen Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yinsheng Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaoyu Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yijun Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Guoyuan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Wei Wang or Guoyuan Chen.

Additional information

These authors contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, W., Zhang, Z., Guo, Y. et al. Carbon disulfide induces mitochondria-mediated apoptosis in Sertoli-germ cells coculture. Mol. Cell. Toxicol. 11, 175–185 (2015). https://doi.org/10.1007/s13273-015-0016-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13273-015-0016-4

Keywords

Search

Navigation