Functional role of caspases in heat-induced testicular germ cell apoptosis

Biol Reprod. 2005 Mar;72(3):516-22. doi: 10.1095/biolreprod.104.034520. Epub 2004 Oct 27.


In the present study, we determined whether a pan caspase inhibitor could prevent or attenuate heat-induced germ cell apoptosis. Groups of five adult (8 wk old) C57BL/6 mice pretreated with vehicle (DMSO) or Quinoline-Val-Asp (Ome)-CH2-O-Ph (Q-VD-OPH), a new generation broad-spectrum caspase inhibitor, were exposed once to local testicular heating (43 degrees C for 15 min) and killed 6 h later. The inhibitor (40 mg/kg body weight) or vehicle was administered intraperitoneally (i.p.) 1 h before local testicular heating. Germ cell apoptosis was detected by TUNEL assay and quantitated as number of apoptotic germ cells per 100 Sertoli cells at stages XI-XII. Compared with controls (16.8 +/- 3.1), mild testicular hyperthermia within 6 h resulted in a marked activation (277.3 +/- 21.6) of germ cell apoptosis, as previously reported by us. Q-VD-OPH at this dose markedly inhibited caspase 3 activation and significantly prevented (by 67.0%) heat-induced germ cell apoptosis. Q-VD-OPH-mediated rescue of germ cells was independent of cytosolic translocation of mitochondrial cytochrome c and DIABLO. Electron microscopy further revealed normal appearance of these rescued cells. Similar protection from heat-induced germ cell apoptosis was also noted after pretreatment with minocycline, a second-generation tetracycline that effectively inhibits cytochrome c release and, in turn, caspase activation. Collectively, the present study emphasizes the role of caspases in heat-induced germ cell apoptosis.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Analysis of Variance
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Caspases / drug effects
  • Caspases / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Germ Cells / enzymology*
  • Hot Temperature*
  • In Situ Nick-End Labeling
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Minocycline / pharmacology
  • Quinolines / pharmacology
  • Testis / cytology
  • Testis / enzymology*


  • Amino Acid Chloromethyl Ketones
  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Quinolines
  • quinoline-val-asp(OMe)-CH2-OPH
  • Caspases
  • Minocycline