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1 December 2000 Redistribution of Bax Is an Early Step in an Apoptotic Pathway Leading to Germ Cell Death in Rats, Triggered by Mild Testicular Hyperthermia
Cindy M. Yamamoto, Amiya P. Sinha Hikim, Phuong N. Huynh, Brian Shapiro, Yanhe Lue, Wael A. Salameh, Christina Wang, Ronald S. Swerdloff
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Abstract

Programmed cell death occurs spontaneously during spermatogenesis and can be induced in a cell- and stage-specific manner by mild testicular hyperthermia. Studies using transgenic mice suggest the involvement of Bcl-2 proteins in regulating germ cell apoptosis. To delineate further the pathways involved, we examined the temporal changes in proapoptotic Bax and antiapoptotic Bcl-2 in rat testes after transient exposure to heat (43°C for 15 min). Germ cell apoptosis, involving exclusively early (I–IV) and late (XII–XIV) stages, was activated within 6 h. Initiation of apoptosis was preceded by a redistribution of Bax from a cytoplasmic to perinuclear localization within 0.5 h of heating as assessed by immunocytochemical methods. In contrast, Bcl-2 is distributed both in the cytoplasm and nucleus in those cell types susceptible to heat-induced apoptosis. Despite the striking redistribution, Bax levels remained unchanged as determined by Western analysis; Bcl-2 levels increased significantly by 6 h after heat exposure. Reverse transcription-polymerase chain reaction analysis indicated no change in either Bax or Bcl-2 mRNA levels in response to heat, suggesting the involvement of post-transcriptional rather than transcriptional mechanisms mediating their activity. The marked subcellular redistribution of Bax prior to activation of apoptosis and the increase in Bcl-2 suggest an involvement of Bcl-2 family members in heat-induced apoptotic death of germ cells.

Cindy M. Yamamoto, Amiya P. Sinha Hikim, Phuong N. Huynh, Brian Shapiro, Yanhe Lue, Wael A. Salameh, Christina Wang, and Ronald S. Swerdloff "Redistribution of Bax Is an Early Step in an Apoptotic Pathway Leading to Germ Cell Death in Rats, Triggered by Mild Testicular Hyperthermia," Biology of Reproduction 63(6), 1683-1690, (1 December 2000). https://doi.org/10.1095/biolreprod63.6.1683
Received: 2 March 2000; Accepted: 1 July 2000; Published: 1 December 2000
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KEYWORDS
Apoptosis
spermatogenesis
stress
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