Cross-Link between Heat Shock Protein Hsp70 and Epigenetic Alterations in Testicular Tissue; Evidence for A Diabetic Condition

Background: Diabetes has been known to adversely affect germ cells and sperm DNA integrity via inducing oxidative stress. The Heat shock (HSP) family proteins are known as stress responders, which are highly expressed in oxidative stress condition. Aside from oxidative stress-induced DNA fragmen-tation, it has been shown that histamine-protamine exchanged failure (epigenetic pathways) is able to negatively affect DNA integrity. Thus, here in the current study, the cross-link between DNA methylation, histone acetylation/deacetylation, and the Hsp70 content of testicles was investigated.Materials and Methods: For this purpose, 12 mature male Wistar rats were divided into control and diabetes-induced groups (No:6 rats in each group). The experimental diabetes was induced by streptozotocin. The germ cells global DNA methylation was assessed by immunohistochemical staining. The mRNA levels of DNA methyltransferase-1 (DNMT1), his-tone acetyltransferase (HAT) and Histone de-acetyltransferase (HDAC) were evaluated by qRT-PCR. The Hsp70 expression was evaluated both at mRNA and protein levels. Finally, the germ cells DNA integrity was analyzed by TUNEL staining.Results: Observations showed a significant (P<0.05) reduction in global DNA methylation in the diabetes-induced group. The animals in the diabetes-induced group represented a remark-able (P<0.05) reduction in mRNA level of HAT, DNMT1, and HDAC versus the control animals. Moreover, the diabe-tes-induced animals exhibited decreased expression of Hsp70 (P<0.05). Finally, the diabetes-induced group showed a severe DNA fragmentation at the germ cell level.Conclusion: Our data showed that simultaneous with de-creased Hsp70 level, the global DNA methylation and mRNA levels of HAT, HDAC and DNMT1 were decreased in diabetic condition. In addition, simultaneous with DNMT1 reduction, the diabetes-induced animals exhibited a remarkable reduction in global DNA methylation and a significant enhancement in DNA fragmentation. All these findings represent a direct cor-relation between Hsp70 expression, epigenetic changes, DNA methylation and DNA fragmentation in the diabetic testicle.

کلیدواژه ها:

Experimental Diabetes ، Epigenetic ، DNA Fragmen-tation ، Hsp70 ، Rat