Cross-Link between Epigenetic Modifications and Hsp70 Expression in Varicocele Condition after Testoster-one Therapy

Background: Epigenetic, with a specific and extensive role in genomic signaling and modifications, has gained interests in many diseases, especially varicocele (VCL). VCL is a well-known male fertility disorder, in which the oxidative stress and failed Hsp70 expression, in the sole and simultaneously, are known to result in germ and sperm cells DNA fragmentation that finally is able to end with temporal and/or complete infertil-ity. Here in the present study, we tried to reveal the cross-link between nuclear DNA-related epigenetic changes and Hsp70-2 expression in varicocele-induced testes, after testosterone therapy.Materials and Methods: For this purpose, 18 mature male Wistar rats were divided into three groups (n=6 for each group), including control (Con), experimental VCL-induced, and testosterone-treated VCL-induced (VCL+T). The Real-time PCR was used to analyze the expressions of DNMT1, HAT, and HDAC, as epigenetic markers, and Hsp70, as stress responder, in all groups. The germ and sperm cells DNA integrity was analyzed by DNA ladder test. Finally, the correlation between epigenetic markers and Hsp70-2 were analyzed.Results: Our observations showed a significant (P<0.05) reduc-tion in DNMT, HAT, HDAC, and Hsp70 in VCL group versus the control animals. However, the HAT, HDAC, DNMT1 and Hsp70 expression were remarkably increased in VCL+T group versus VCL animals. Moreover, the animals in VCL+T group represented ameliorated DNA fragmentation (at both germ and sperm cells) versus VCL-sole animals.Conclusion: Observations revealed that testosterone, by boost-ing the Hsp70 expression, ameliorates the VCL-induced disin-tegrity. On the other hand, promoted Hsp70 expression, in turn, amplifies the epigenetic markers. Thus, the testosterone could stabilize and/or protect the DNA content by retaining the Hsp70 and epigenetic markers.

کلیدواژه ها:

Varicocele ، HAT HDAC ، DNMT1 ، Hsp70 ، Testoster-one