Skip to main content
SpringerLink
Log in

Simulated microgravity activates apoptosis and NF-κB in mice testis

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Microgravity is known to have significant effect on all aspects of reproductive function in animal models. Recent studies have also shown that microgravity induces changes at the cellular level, including apoptosis. Our effort here was to study the effect of simulated microgravity on caspase-8 and the caspase-3 activities, the effectors of the apoptotic pathway and on the transcription factor NF-κB a signaling molecule in mouse testis. Morey-Holton hind limb suspension model was used to simulate microgravity. Caspase-8 and 3 fluorometric assays were carried out and HLS mice testis exhibited a 51% increase in caspase-8 and caspase-3 compared to the controls. A sandwich ELISA-based immunoassay was carried out for detection of NF-κB which again significantly increased in the test mice. Testosterone levels were measured using an ELISA kit and in HLS mice the decrease was significant. There was also a significant decrease in testis weight in the test mice. Simulated microgravity activates caspase 8, 3 and NF-κB necessary to stimulate the apoptotic pathway in mice testis. This may account for the drop in testis weight and testosterone level further affecting testicular physiology and function.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Tou J, Ronca A, Grindeland R, Wade C (2002) Models to study gravitational biology of mammalian reproduction. Biol Reprod 67:1681–1687

    Article  PubMed  CAS  Google Scholar 

  2. Moody S, Gorwill R (2000) Developmental biology research in space: issues and directions in the era of the International Space Station. Dev Biol 228:1–5

    Article  PubMed  CAS  Google Scholar 

  3. Gretebeck R, Greenleaf J (1999) Utility of ground-based simulations of weightlessness. In: Lane HW (ed) Nutrition in space flight and weightlessness models. CRC Press, New York, pp 69–96

    Google Scholar 

  4. Morey-Holten ER, Globus RK (2002) The hindlimb unloading rodent model: technical aspects. J Appl Physiol 92:1367–1377

    Article  CAS  Google Scholar 

  5. Amann R, Deaver D, Zirkin B et al (1992) Effects of microgravity or simulated launch on testicular function in rats. J Appl Physiol 73(Suppl):S174–S185

    Google Scholar 

  6. Philpott D, Sapp W, Williams C, Stevenson J, Black S, Corbett R (1985) Reduction of the spermatogonial population in rat testis flown on space lab-3. Physiologist 28(Suppl):S211–S212

    PubMed  CAS  Google Scholar 

  7. Plakhta-Plakutina G, Serova L, Dreval A, Tarabrin S (1976) Effect of 22 days space flight factors on the state of the sex glands and reproductive capacity of rats. Kosm Biol Aviakosam Med 10:40–47

    Google Scholar 

  8. Strollo F (1999) Hormonal changes in humans during space flight. Adv Space Biol Med 7:99–129

    Article  PubMed  CAS  Google Scholar 

  9. Serova L, Denisova L, Baikova O (1989) The effect of microgravity on the reproductive function of male rats. Physiologist 32(Suppl):S29–S30

    PubMed  CAS  Google Scholar 

  10. Perkins ND (2007) Integrating cell-signalling pathways with NF-κB and IKK function. Nat Rev 8:49–62

    Article  CAS  Google Scholar 

  11. Armstrong JW, Kirby-Dobbels K, Chapes SK (1995) The effects of rM-CSF and rIL-6 therapy on immunosuppressed antiorthostatically suspended mice. J Appl Physiol 78:968–975

    PubMed  CAS  Google Scholar 

  12. Armstrong JW, Nelson KA, Simske SJ, Luttges MW, Landolo JJ, Chapes SK (1993) Skeletal unloading causes organ specific changes in immune cell responses. J Appl Physiol 75:2734–2739

    PubMed  CAS  Google Scholar 

  13. Chapes SK, Mastro AM, Sonnenfeld G, Berry WD (1992) Anti orthostatic suspension as a model for the effects of spaceflight on the immune system. J Leukoc Biol 54:227–235

    Google Scholar 

  14. Rehman J, Christ G, Alyskewycz M, Kerr E, Melman A (2000) Experimental hyper prolactinemia in a rat model: alteration in centrally mediated neuroerectile mechanisms. Int J Impot Res 12:23–32

    Article  PubMed  CAS  Google Scholar 

  15. Stennicke HR, Salvesen GS (1998) Properties of the caspases. Biochim Biphys Acta 1387:17–31

    CAS  Google Scholar 

  16. Takahashi A, Alnemri ES, Lazebnik YA et al (1996) Cleavage of lamin A by Mch2, but not CPP32: multiple interleukin 1 beta-converting enzyme related proteases with distinct substrate recognition properties are active in apoptosis. Proc Natl Acad Sci 93:8395–8400

    Article  PubMed  CAS  Google Scholar 

  17. Stein TP (2002) Space flight and oxidative stress. Nutrition 10:867–871

    Article  Google Scholar 

  18. Hadley JA, Hall JC, O’Brien A, Ball R (1992) Effects of a simulated microgravitymodel on cell structure and function in rat testis and epididymis. J Appl Physiol 72:748–759

    PubMed  CAS  Google Scholar 

  19. Zhou DX, Qiu SD, Wang ZY, Zhang J (2006) Effect of tail-suspension on the reproduction of adult male rats. Zhonghua Nan Ke Xue 12:326–329

    PubMed  CAS  Google Scholar 

  20. Mendis-Handagama SM, Watkins PA, Gelber SJ, Scallen TJ (1998) The effect of chronic luteinizing hormone treatment on adult rat Leydig cells. Tissue Cell 30:64–73

    Article  PubMed  CAS  Google Scholar 

  21. Jannini EA, Ulisse S, Piersanti D et al (1993) Early thyroid hormone treatment in rats increases testis size and germ cell number. Endocrinology 132:2726–2728

    Article  PubMed  CAS  Google Scholar 

  22. Cooke PS (1991) Thyroid hormones and testis development: a model system for increasing testis growth and sperm production. Ann N Y Acad Sci 637:122–132

    Article  PubMed  CAS  Google Scholar 

  23. Francavilla S, D’Abrizio P, Rucci N et al (2000) Fas and Fas ligand expression in fetal and adult human testis with normal or deranged spermatogenesis. J Clin Endocrinol Metab 85:2692–2700

    Article  PubMed  CAS  Google Scholar 

  24. Kierzenbaum A (2001) Apoptosis during spermatogenesis: the thrill of being alive. Mol Reprod Dev 58:1–3

    Article  Google Scholar 

  25. Scaffidi C, Fulda S, Srinivasan A et al (1998) Two CD 95 (APO-1/Fas) signaling pathways. EMBO J 17:1675–1678

    Article  PubMed  CAS  Google Scholar 

  26. Hengartner MO (2000) The biochemistry of apoptosis. Nature 407:770–776

    Article  PubMed  CAS  Google Scholar 

  27. Tesaric J, Martinez F, Rienzi L et al (2002) In-vitro effects of FSH and testosterone withdrawal on caspase activation and DNA fragmentation in different cell types of human seminiferous epithelium. Hum Reprod 17:1811–1819

    Article  Google Scholar 

  28. Smithwich EB, Young LG (2001) Effects of androgen deprivation on the histology of adult chimpanzee testis. Tissue Cell 33:262–272

    Article  Google Scholar 

  29. Blockers TM, Nieschlag E, Kreutz MR, Bergmann M (1994) Localization of follicle stimulating hormone (FSH) immunoreactivity and hormone receptor mRNA in testicular tissue of infertile men. Cell Tissue Res 278:595–600

    Article  Google Scholar 

  30. Kim JM, Ghosh SR, Weil AC, Zirkin BR (2001) Caspase-3 and caspase activated deoxyribonuclease are associated with testicular germ cell apoptosis resulting from reduced testicular testosterone. Endocrinology 142:3801–3816

    Google Scholar 

  31. Lee J, Richburg JH, Shipp EB, Meistrich ML, Bockelheide K (1999) The Fas system, a regulator of testicular germ cell apoptosis is differentially up-regulated in Sertoli cell versus germ cell injury of the testis. Endocrinology 140:852–858

    Article  PubMed  CAS  Google Scholar 

  32. Pentikainen V, Erkkila K, Dunkel L (1999) Fas regulates germ cell apoptosis in the human testis in vitro. Am J Physiol 276:E310–E316

    PubMed  CAS  Google Scholar 

  33. Tapanainen JS, Tilly JL, Vihko KK, Hsueh AJ (1993) Hormonal control of apoptotic cell death in the testis: gonadotropins and androgens as testicular cell survival factors. Mol Endocrinol 7:643–650

    Article  PubMed  CAS  Google Scholar 

  34. Troiano L, Fustini MF, Lovato E et al (1994) Apoptosis and spermatogenesis: evidence from an in vivo model of testosterone withdrawal in the adult rat. Biochem Biophys Res Commun 202:1315–1321

    Article  PubMed  CAS  Google Scholar 

  35. Henriksen K, Hakovirta H, Parvinen M (1995) Testosterone inhibits and induces apoptosis in rat seminiferous tubules in a stage-specific manner: in situ quantification in squash preparations after administration of ethane dimethane sulfonate. Endocrinology 136:3285–3291

    Article  PubMed  CAS  Google Scholar 

  36. Yin Y, Stahl BC, DeWolf WC, Morgentaler A (1998) Heat-induced testicular apoptosis occurs independently of hormonal depletion. Apoptosis 3:281–287

    Article  PubMed  CAS  Google Scholar 

  37. Blackburn DM, Gray AJ, Lioyd SC, Sheard CM, Foster PMD (1988) Comparison of the effects of the three isomers of dinitrobenzene on the testis in the rat. Toxicol Appl Pharmacol 92:54–64

    Article  PubMed  CAS  Google Scholar 

  38. Muguruma M, Yamazaki M, Okamura M, Moto M, Kashida Y, Mitsumori Y (2005) Molecular mechanism on the testicular toxicity of 1,3-dinitrobenzene in Sprague-Dawley rats: preliminary study. Arch Toxicol 79:729–736

    Article  PubMed  CAS  Google Scholar 

  39. Kucharczak J, Simmons MJ, Fan YJ, Ge´ linas C (2003) To be, or not to be: NFkB is the answer—role of Rel/NF-kB in the regulation of apoptosis. Oncogene 22:8961–8982

    Article  PubMed  CAS  Google Scholar 

  40. Rocha S, Campbell KJ, Perkins ND (2003) p53 and Mdm2-independent repression of NF-kB transactivation by the ARF tumor suppressor. Mol Cell 12:15–25

    Article  PubMed  CAS  Google Scholar 

  41. Rocha S, Garrett MD, Campbell KJ, Schumm K, Perkins ND (2005) Regulation of NF-kB and p53 through activation of ATR and Chk1 by the ARF tumour suppressor. EMBO J 24:1157–1169

    Article  PubMed  CAS  Google Scholar 

  42. Campbell KJ, Rocha S, Perkins ND (2004) Active repression of antiapoptotic gene expression by ReIA(p65) NF-kB. Mol Cell 13:853–865

    Article  PubMed  CAS  Google Scholar 

  43. Papa S, Bubici C, Zazzeroni F et al (2006) The NF-kappaB-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease. Cell Death Differ 13:712–729

    Article  PubMed  CAS  Google Scholar 

  44. Nakano H, Nakajima A, Sakon-Komazawa S, Piao JH, Xue X, Okumura K (2006) Reactive oxygen species mediate crosstalk between NF-kappaB and JNK. Cell Death Differ 13:730–737

    Article  PubMed  CAS  Google Scholar 

  45. Vousden KH, Lu X (2002) Live or let die: the cells response to p53. Nat Rev Cancer 2:594–604

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by NASA NCC 9-165: NIH 1P20MD001822-1 (GR).

Author information

Authors and Affiliations

  1. Department of Biology, Molecular Toxicology Laboratory, Center for Biotechnology & Biomedical Sciences, Norfolk State University, Norfolk, VA, 23504, USA

    Chidananda S. Sharma, Prabakaran Ravichandran, Vani Ramesh, Joseph C. Hall & Govindarajan T. Ramesh

  2. NASA University Research Center, Texas Southern University, Houston, TX, 77004, USA

    Shubhashish Sarkar, Adaikkappan Periyakaruppan, Bindu Sadanandan, Renard Thomas, Bobby L. Wilson & Govindarajan T. Ramesh

Authors
  1. Chidananda S. Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shubhashish Sarkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adaikkappan Periyakaruppan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Prabakaran Ravichandran
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bindu Sadanandan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vani Ramesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Renard Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Joseph C. Hall
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bobby L. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Govindarajan T. Ramesh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Govindarajan T. Ramesh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sharma, C.S., Sarkar, S., Periyakaruppan, A. et al. Simulated microgravity activates apoptosis and NF-κB in mice testis. Mol Cell Biochem 313, 71–78 (2008). https://doi.org/10.1007/s11010-008-9743-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-008-9743-3

Keywords

Search

Navigation