Key apoptotic pathways for heat-induced programmed germ cell death in the testis

Endocrinology. 2003 Jul;144(7):3167-75. doi: 10.1210/en.2003-0175.

Abstract

Short-term exposure (43 C for 15 min) of the rat testis to mild heat results within 6 h in stage- and cell-specific activation of germ cell apoptosis. Initiation of apoptosis was preceded by a redistribution of Bax from a cytoplasmic to paranuclear localization in heat-susceptible germ cells. Here we show that the relocation of Bax is accompanied by cytosolic translocation of cytochrome c and is associated with activation of the initiator caspase 9 and the executioner caspases 3, 6, and 7 and cleavage of poly(ADP) ribose polymerase. Furthermore, early in apoptosis, a significant amount of Bax also accumulates in endoplasmic reticulum, as assessed by Western blot analyses of fractionated testicular lysates. In additional studies using the FasL-defective gld mice, we have shown that heat-induced germ cell apoptosis is not blocked, thus providing evidence that the Fas signaling system may be dispensable for heat-induced germ cell apoptosis in the testis. Taken together, these results demonstrate that the mitochondria- and possibly also endoplasmic reticulum-dependent pathways are the key apoptotic pathways for heat-induced germ cell death in the testis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Caspase 3
  • Caspase 6
  • Caspase 7
  • Caspase 9
  • Caspases / metabolism
  • Cytochrome c Group / metabolism
  • Cytosol / metabolism
  • Endoplasmic Reticulum / metabolism
  • Fas Ligand Protein
  • Hot Temperature
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Microscopy, Electron
  • Mitochondria / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2*
  • Rats
  • Rats, Sprague-Dawley
  • Spermatocytes / enzymology*
  • Spermatocytes / ultrastructure
  • Testis / cytology*
  • Testis / enzymology
  • bcl-2-Associated X Protein

Substances

  • Bax protein, mouse
  • Bax protein, rat
  • Cytochrome c Group
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Faslg protein, rat
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Poly(ADP-ribose) Polymerases
  • Casp3 protein, mouse
  • Casp3 protein, rat
  • Casp6 protein, mouse
  • Casp6 protein, rat
  • Casp7 protein, mouse
  • Casp9 protein, mouse
  • Casp9 protein, rat
  • Caspase 3
  • Caspase 6
  • Caspase 7
  • Caspase 9
  • Caspases