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This version published online on April 10, 2003
Endocrinology, doi:10.1210/en.2003-0175
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Submitted on February 6, 2003
Accepted on April 4, 2003

Key Apoptotic Pathways for Heat-induced Programmed Germ Cell Death in the Testis

Amiya P. Sinha Hikim1*, Yanhe Lue1, Cindy M. Yamamoto1, Yanira Vera1, Susana Rodriguez1, Pauline H. Yen1, Kevin Soeng1, Christina Wang1, and Ronald S. Swerdloff1

1 Division of Endocrinology, Departments of Medicine and Pediatrics, Harbor-UCLA Medical Center and Research and Education Institute, Torrance, California 90509

* To whom correspondence should be addressed. E-mail: hikim{at}gcrc.rei.edu.

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 PARP. Furthermore, early in apoptosis, a significant amount of Bax also accumulates in endoplasmic reticulum (ER) 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 ER-dependent pathways are the key apoptotic pathways for heat induced germ cell death in the testis.
Key words: Apoptosis • Bax • mitochondria • cytochrome c • caspases • testis




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