Testosterone amplifies HSP70-2a, HSP90 and PCNA expression in experimental varicocele condition: Implication for DNA fragmentation.

The DNA fragmentation and failure in post-meiotic maturation of the spermatozoa because of testosterone withdrawal can affect the fertilization potential in varicocele (VCL) patients. To find out the exact mechanism of VCL-induced failure in histone-protamine replacement process and DNA fragmentation, the correlations between the levels of expression of HSP70-2a, HSP90, PCNA, TP1/2 and PCNA genes and the patterns of DNA methylation were investigated before and after testosterone administration in rats. In total, 40 mature male Wistar rats (10 in each group) were assigned between control (with no intervention), control-sham (undergone a simple laparotomy), VCL-induced (VCL-sole), and testosterone-treated VCL-induced (VCLT) groups. The HSP70-2a, HSP90, PCNA, TP1, and TP2 genes expressions and the patterns of global DNA methylation were determined in all groups. A statistically significant (p < 0.05) reduction were found in the HSP70-2a, HSP90, PCNA, TP1 and TP2 genes expressions in VCL-sole group. In VCLT group, testosterone was shown to significantly (p < 0.05) up-regulate the HSP70-2a, HSP90, PCNA, and TP2expression levels, but TP1 expression has not been changed. Furthermore, the VCLT group exhibited higher DNA methylation rates compared to VCL-sole animals. In conclusion, testosterone, by up-regulating the HSP70-2a and HSP90 expressions and maintaining the pre-existing HSP70-2a and HSP90 proteins levels, may be the reason for the significant increment in TP2 expression during post-meiotic stage and can boost the global methylation rates of DNA via up-regulating the PCNA expression, suggesting that administration of testosterone can mitigate the VCL-impaired histone-protamine replacement and DNA methylation rates and protect the cellular DNA content from VCL-induced oxidative stress.