Effect of Experimental Varicocele on DNA Methylation and Histone Acethylation in Testicular Tissue

Background: The varicocele (VCL) has been known as the main reason of male infertility. It has been illustrated that, the VCL negatively affects spermatogenesis via inducing oxidative stress, suppressing testicular endocrine status and heat dependent apoptosis and consequently results in severe DNA damage at sperm level. However, the roles of different genes/proteins in relation with DNA methylation and histone acethylation during spermatogenesis has not been established, yet. Thus, present study was done in order to clarify, whether the VCL affects the epigenetic elements or not Methods: For this purpose, 18 mature male Wistar rats (180±20 gr) were divided into control, control-sham and VCL-induced groups. The animals in the control-sham group were undergone simple laparotomy and no surgical interventions were performed in the control group.Following 60 days, the animals were euthanized and the testicles were dissected out. The mRNA levels of DNA (cytosine-5)-methyltransferase 1 (DNMT1), histone acetyltransferases (HATs) and histone deacetylases (HDAC) were analyzed using RT-PCR. Moreover, the 5-methylcytosine (5-mc) staining was done to assay the methylation ratio. Results: Observations revealed a significant (P<0.05) reduction in expressions of DNMT1, HATs and HDAC in varicocele-induced animals versus control and control-sham groups. Moreover, the animals in VCL-induced group exhibited diminished 5-mc+ cells distribution per mm2 of testicular tissue. Conclusion: Our data showed that, the VCL bydown-regulating the expression of DNMT1, HATs and HDAC, as key genes involving in testicular epigenetic, affects the DNA methylation and histone acethylation ratios.

کلیدواژه ها:

Varicocele ، DNMT1 ، HATs ، HDAC ، DNA methylation ، Histone acethylation