DNA hypomethylation predisposes sperm to DNA damage in individuals with varicocele

Abstract

This study aimed to assess and compare global DNA methylation (GDM) between fertile men and infertile men with varicocele. In addition, we evaluated the correlations between DNA methylation with reactive oxygen species (ROS), protamine deficiency, and DNA integrity. Semen samples were collected from 44 men with grades II and III varicocele, and 15 fertile men for assessment of semen parameters, DNA methylation, DNA fragmentation, oxidative stress, and protamine deficiency. Samples were evaluated by the World Health Organization (WHO) criteria, immunostaining, the TUNEL assay, 2 0 , 7 0 -dichlorodihydrofluorescein diacetate (DCFH-DA) staining, and chromomycin A3 (CMA3) staining. Semen parameters were significantly lower in individuals with varicocele compared to fertile men. The percentage of GDM and intensity of DCFH were reduced and the percentages of DCFH, TUNEL, and CMA3 positive sperm significantly increased in individuals with varicocele compared to fertile men. Correlation analysis revealed a negative significant relation between DNA methylation and DNA fragmentation, but not with the degree of protamine deficiency and ROS production. The results have shown that individuals with varicocele show increased DNA susceptibility to damage when DNA is hypomethylated. This phenomenon appears to be independent of ROS production.

Comparison of Oxidative Stress Intensity in the Seminal Plasma and Serum of Infertile Patients with Different Varicocele Grades and Subjects with No Varicocele: A Cross-Sectional Study

“…In this study, patients with varicocele had significantly low sperm and total sperm counts, compared with nonvaricocele subjects. These results are consistent with previous studies, which reported abnormalities in the semen parameters of varicocele patients (19)(20)(21). Our findings also revealed that a higher grade of varicocele is associated with reduced sperm count and volume; the G3 group had a lower sperm and semen volume, compared to other groups.…”

The effect of vitamin E & vitamin B on sperm function in rat varicocele model

“…Previous studies demonstrated that heat-related oxidative stress or protamine deficiency in varicocele condition prone spermatozoa to DNA fragmentation (Bahreinian et al, 2015;Ni et al, 2016). In this study, we observed a significant reduction in percentage of residual histone in varicocelized rats that received Vit B+Vit E compared with varicocelized rats that received water at 4 months.…”

One‐carbon cycle support rescues sperm damage in experimentally induced varicocoele in rats

“…Finally, we have previously shown in humans that varicocoele induces a state of DNA hypo-methylation that predisposes to DNA damage [12] and that is overcome by varicocoelectomy [13]. Singh et al [14] explain how the one-carbon cycle provides activated methyl groups necessary for the methylation of DNA and proteins, affecting both gene expression and protein function.…”