Sperm concentration, DNA fragmentation, protamine deficiency, and oxidative stress improved after surgery by 42.5%, 47.2%, 18.5%, respectively. No significant differences in percentage of sperm motility, global DNA methylation, and intensity of DNA methylation following surgery.
DNA hypomethylation predisposes sperm to DNA damage in individuals with varicocele
Men with varicoceles demonstrated lower sperm concentration (35.8 vs. 78.9 M/mL) and motility (43.1% vs. 57.3%). Having a varicocele was associated with a higher abundance of ROS (assessed with 2′, 7′-dichlorodihydrofluorescein staining: 46.8% vs. 29.3%), more protamine deficiency (assessed with chromomycin A3 staining: 43.5% vs. 32.8%), and DNA fragmentation (assessed with TUNEL assay: 13.2% vs. 8.9%). There was a negative correlation between DNA methylation and DNA fragmentation (r = −0.3).
The relationship among sperm global DNA methylation, telomere length, and DNA fragmentation in varicocele: A cross-sectional study of 20 cases
DNA fragmentation and telomere length were not statistically different between the two groups. Global sperm DNA methylation was lower in men with varicoceles compared to controls; however, this did not achieve statistical significance.
Differential DNA methylation pattern and sperm quality in men with varicocele
The genomes of men with varicoceles were globally hypomethylated, when compared to the control group (). 1,695 statistically significant differentially methylated regions were identified in the varicocele group compared with the controls.
Men with grade II or III varicoceles demonstrated lower levels of global DNA methylation compared to those with grade I varicoceles, though this did not achieve statistical significance.
Molecular basis for varicoceles
Is methylenetetrahydrofolate reductase (MTHFR) gene A1298C polymorphism related with varicocele risk?
There was no significant difference in the frequency of C677T genotypes between patients with varicocele and healthy controls; the MTHFR-1298/A allele frequency in the varicocele group was statistically significantly higher in comparison to the control group. Men with a homozygous genotype (1298AA) for the polymorphic allele A1298C have a 2.3-fold higher risk of having varicocele compared with men who do not have this genotype (OR = 2.3, ).
Increased de novo DNA methylation enzymes in sperm of Individuals with varicocele
Similar percentage of DNMT1 positive sperm between the two groups; the percentage of DNMT3A and DNMT3B positive sperm were significantly higher in the varicocele group compared to the fertile control group (3A: 65.4% vs. 48.3%; 3B: 76.6% vs. 64.3%). Similar results at the RNA level were found.
Animal studies
Effects of varicocele on DNA methylation pattern of H19 and Snrpn gene in spermatozoa and behavioural characteristics of adult rat offspring
There were no significant differences in DNA methylation levels of H19 and Snrpn genes in spermatozoa among the control group, sham operation group, or varicocele-induced group.
Aberrant expression of TET2 accounts for DNA hypomethylation in varicocele
Rats in the varicocele group demonstrated decreased sperm concentration, motility, and morphology; chromatin maturity and DNA integrity (assessed by degree of DNA damage) compared to the other groups.
