Methylation patterns of methylenetetrahydrofolate reductase gene promoter in infertile males.

Errors of folate/homocysteine pathways which are critical for transferring methyl groups have been suggested to affect male fertility. We aimed to evaluate the methylation patterns of the promoter of methylenetetrahydrofolate reductase (MTHFR) gene in infertile males and to investigate the association between MTHFR promoter methylation and success of sperm retrieval. Thirty-five nonobstructive azoospermic and 46 severe oligozoospermic patients constituted the study group and were compared with 49 fertile and/or normozoospermic men. The methylation status was analysed by methylation-specific polymerase chain reaction. MTHFR promoter methylation was detected in infertile men with NOA and SO in the ratio of 48.6% and 58.7%, respectively. Methylation was also observed in 51% of controls. MTHFR promoter was methylated in 65% of men with viable spermatozoon during TESE. No association was found regarding to the profile of MTHFR promoter methylation between both NOA and SO patients and controls (p = .621). There was no relation between the methylation status of MTHFR promoter and low motility and poor morphology (p = .682 and p = .413, respectively). No association was found between MTHFR promoter methylation and presence of viable spermatozoa (p = .382). Our data indicate that the promoter methylation of MTHFR gene may not be associated with male infertility.

Partial Deletions of Y-Chromosome in Infertile Men with Non-obstructive Azoospermia and Oligoasthenoteratozoospermia in a Turkish Population.

Many genetic alterations have been identified to aid in understanding the genetic basis of male infertility, however, the cause of 30% of male infertility remains unknown. Some studies indicated that subdeletions of Y chromosome may be a reason for male infertility caused by testicular failure. In this regard, we aimed to investigate frequency of AZFc region subdeletions and their clinical effects in patients with idiopathic infertility. A total of 333 male infertile patients with non-obstructive azoospermia (NOA) or oligoasthenoteratozoospermia (OAT), and 87 normozoospermic controls were screened to detect gr/gr, b1/b3 and b2/b3 subdeletions. We recorded higher gr/gr deletion frequency in normozoospermic controls compared NAO and OAT groups (p=0.026). There were no significant differences in b2/b3 subdeletion rates among groups (p=0.437). In the OAT group, follicle-stimulating hormone levels of cases with b2/b3 deletion were statistically lower than cases without b2/b3 deletion (p=0.047). No statistical correlations were indicated among subdeletions, sperm count and assisted reproductive technology (ART) outcomes. These data demonstrate that gr/gr and b2/b3 subdeletions may not play a significant role in the etiopathogenesis of male infertility and ART outcomes in the studied population.

The role of epigenetics in spermatogenesis.

Male germ cells have a unique morphology and function to facilitate fertilization. Sperm deoxyribonucleic acid (DNA) is highly condensed to protect the paternal genome during transfer from male to oocyte. Sperm cells undergo extensive epigenetic modifications during differentiation to become a mature spermatozoon. Epigenetic modifications, including DNA methylation, histone modifications, and chromatin remodeling are substantial regulators of spermatogenesis. DNA hypermethylation is associated with gene silencing. Meanwhile, hypomethylation is associated with gene expression. In sperm cells, promoters of developmental genes are highly hypomethylated. Proper DNA methylation is essential for embryo development. Histone modifications are chemical modifications that change the DNA-binding capacity of histones and the accessibility of regulatory factors to the DNA, thereby altering gene expression. Phosphorylation, methylation, acetylation, and ubiquitination are primary modifications of lysine and serine residues on histone tails. In addition to somatic histones, testis-specific histone variants are expressed, including histone H2B in mature sperm. The replacement of histones with protamines is a crucial step in spermatogenesis. Histone hyper-acetylation induces a loose chromatin structure and facilitates topoisomerase-induced DNA strand breaks. As a result, histones are replaced with transition proteins. Next, the transition proteins are replaced with protamines that induce compaction of sperm DNA. This review provides an overview of epigenetic changes during spermatogenesis.