Sperm epigenetic features and a methyl donor: a randomized control trial study

Background: Folic acid is an important intermediary in the transfer of methyl groups in the synthesis of DNA, stability and integrity. But, the administration of this has not been investigated with the approach to improve the status of methylation in patients with sperm disorders.Objective: Therefore, the aim of this study was to determine the optimization of sperm parameters and chromatin parameters, global DNA methylation level of sperm genomes and improvement the transcription retention of DNA methyltransferases (DNMTs).Materials and Methods: This study is a randomized, controlled clinical trial. A number of 30 subjects with normal parameters were studied as the control group. Also, 30 subjects were selected for sperm analysis with parameters less than WHO criteria and randomly divided to two intervention treatment. In the two-drug group, vitamin E was given at a dose of 400 mg and selenium 200 mg daily and in the three-drug group, vitamin E 400 mg, selenium 200 mg and folic acid at a dose of 5 mg were prescribed daily (n=15/each group). After three months like before intervention, cytochemical tests were performed to evaluate the quality of chromatin and DNA of the sperm. Samples were compared using qRT PCR for DNMT1, 3A and 3B expression. The percentage of global DNA methylation was also evaluated based on ELISA.Results: Sperm parameters such as concentration, progressive movement, normal morphology and viability were significantly higher in the three-drug group. The sperm decondensation and fragmentation of sperm DNA in the three-drug group was significantly lower than that of two-drug group. The global methylation of sperm DNA in the three-drug group was significantly reduced compared to pre- intervention. The increased global methylation was associated with a reduction in sperm parameters and chromatin integrity. The expression of DNMTs was not affected by the intervention.Conclusion: The use of folic acid was able to improve sperm quality and epigenetic features in terms of decreasing the status of global methylation, increasing the chromatin and DNA integrity and also improving the sperm parameters.

کلیدواژه ها:

Methyltransferases expression ، Sperm ، Global methylation ، Chromatin