Effects of hyperthermia on spermatogenesis, apoptosis, gene expression, and fertility in adult male mice

Testicular heat shock was used to characterize cellular and molecular mecha nisms involved in male fertility. This model is relevant because heat shock proteins (HSPs) are required for spermatogenesis and also protect cells fr om environmental hazards such as heat, radiation, and chemicals. Cellular a nd molecular methods were used to characterize effects of testicular heat s hock (43 degreesC for 20 min) at different times posttreatment. Mating stud ies confirmed conclusions, based on histopathology, that spermatocytes are the most susceptible cell type. Apoptosis in spermatocytes was confirmed by TUNEL, and was temporally correlated with the expression of stress-inducib le Hsp70-1 and Hsp70-3 proteins in spermatocytes. To further characterize g ene expression networks associated with heat shock-induced effects, we used DNA microarrays to interrogate the expression of 2208 genes and thousands more expression sequence tags expressed in mouse testis. Of these genes, 27 were up-regulated and 151 were down-regulated after heat shock. Array data were concordant with the disruption of meiotic spermatogenesis, the heat-i nduced expression of HSPs, and an increase in apoptotic spermatocytes. Furt hermore, array data indicated increased expression of four additional non-H SP stress response genes, and eight cell-adhesion, signaling, and signal-tr ansduction genes. Decreased expression was recorded for 10 DNA repair and r ecombination genes; 9 protein synthesis, folding, and targeting genes; 9 ce ll cycle genes; 5 apoptosis genes; and 4 glutathione metabolism genes. Thus , the array data identify numerous candidate genes for further analysis in the heat-shocked testis model, and suggest multiple possible mechanisms for heat shock-induced infertility.