Testis

Mitochondria-Dependent Pathway Is Involved in Heat-Induced Male Germ Cell Death: Lessons from Mutant Mice

Abstract
The signaling events leading to apoptosis can be divided into two major pathways, involving either mitochondria (intrinsic) or death receptors (extrinsic). In a recent study, we have shown the involvement of the mitochondria-dependent apoptotic pathway in heat-induced male germ cell apoptosis in the rat. In additional studies, using the gld and lpr ^cg mice, which harbor loss-of-function mutations in Fas L and Fas, respectively, we have shown that heat-induced germ cell apoptosis is not blocked, thus providing evidence that the Fas signaling system is not required for heat-induced germ cell apoptosis in the testis. In the present study, we have found that the initiation of apoptosis in wild type mice was preceded by a redistribution of Bax from a cytoplasmic to paranuclear localization in heat-susceptible germ cells. The relocation of Bax is accompanied by sequestration of ultra-condensed mitochondria into paranuclear areas of apoptotic germ cells, cytosolic translocation of mitochondrial cytochrome c and DIABLO and is associated with activation of the initiator caspase 9 and the executioner caspase 3. Similar events were also noted in both gld and lpr ^cg mice. Taken together, these results indicate that the mitochondria-dependent pathway is the key apoptotic pathway for heat induced male germ cell death in mice.

Key words: Male Reproductive Tract • Testis • Apoptosis • Spermatogenesis

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