Impaired DNA Demethylation in Germ Cells CloselyDepends on Suppressed TET Proteins Expression Level inAn Experimental Varicocele Condition

Background: Failed dynamic DNA methylation and demethylationcollaboratively with a genomic integrity has beenshown to remarkably affect the sperm potential in maintainingmale fertility in varicocele subjects. Ten-Eleven Translocationproteins (۱-۳) (TET ۱-۳) are known to activate the DNA demethylationprocess by oxidizing ۵-methylcytosine (۵mC) inthe pachytene spermatocytes, round and elongated spermatids.The TET enzymes role in pluripotency, differentiation, development,and meiosis is well documented. The current s tudy wasaimed to inves tigate the effect of varicocele on expression levelsof TETs (۱-۳) in the tes ticular tissue.Materials and Methods: For this purpose, ۱۲ male matureWis tar rats were divided into control and varicocele-inducedgroups (n=۶/group). The experimental varicocele was inducedby partially ligating the left renal vein. Following four months,the left tes ticles were dissected out and the mRNA levels ofTET proteins (۱-۳), as well as the TET (۱-۳) + spermatocytesand spermatids, were evaluated by immunohis tochemical s tainingtechniques.Results: In the varicocele-induced group the mRNA levelsof TET ۲, and ۳ were decreased, however, the TET۱ enzymemRNA expression was increased. Moreover, the mean dis tributionsof TET ۱, ۲, ۳+ spermatocytes and spermatids were decreasedin the varicocele-induced group.Conclusion: Minding TET۱ role in regulating pluripotency ofspermatogonia, its high mRNA levels could be related to maintenanceof pluripotency of the s tem cells. However, developingfull spermatogenesis requires all TET enzyme types. Thus,failed spermatogenesis in varicocele conditions could be due tothe lack of TET proteins that leads to impaired DNA methylation/demethylation balance among all germ cell types

کلیدواژه ها:

Varicocele ، TET Proteins ، Spermatogenesis ، DNADemethylation