Mitochondrial DNA polymerase gamma gene polymorphism is not associated with male infertility

Abstract

Purpose CAG repeat length of human miotochondrial DNA Polymerase gamma (POLG) gene is polymorphic with a major allele at 10 repeats and considered as the common allele whereas the mutant alleles (not 10/not 10 CAG repeats) were found to be associated with oligospermia / oligoasthenospermia in male infertility. To explore whether CAG trinucleotide repeat expansion in exon 1 of POLG gene is associated with spermatogenic failure. Methods One hundred twenty four infertile men (sperm count <20 million/ml) and 60 normozoospermic (sperm count >20 million/ml) control Indian men of Tamil Nadu, were enrolled. DNA was extracted from 10 ml of peripheral blood and from semen using standard procedures. CAG repeat expansion was analyzed by polymerase chain reaction. Amplified products were quantified by 2 % agarose gel electrophoresis and subjected to genescan analysis to ascertain the size of POLG-CAG alleles. Results This analysis interestingly revealed that the common allele 10 (10-CAG repeats) was widespread in infertile and normozoospermic control men with a frequency of 79 % and 71.7 % respectively. No statistical significance was found in POLG genotypic frequency distribution between infertile men and normospermic men. Conclusion The present study confirmed no association between the POLG gene polymorphism and male infertility. Thus, if associated with infertility, the POLG gene polymorphism should be only considered as a minor possible contributing factor in infertile male patients with no impact on obtaining a pregnancy.

Mitochondrial disease and endocrine dysfunction

“…Both hypogonadotrophic and hypergonadotrophic hypogonadism have been described in male patients with MNGIE [69,75]. It was postulated that POLG mutations might be a cause of male infertility, but more recent studies have not confirmed an association between POLG mutations and oligo-azoospermia [91][92][93]. There was no testicular dysfunction in male patients with Perrault syndrome or AARS2 mutations, despite the presence of ovarian insufficiency in female patients with the same mutations [78,88].…”

Epigenetics and male reproduction: the consequences of paternal lifestyle on fertility, embryo development, and children lifetime health

“…Despite the identification of several rare genetic variants associated to disruption of spermatogenesis, so far, the only two categories of genetic alterations responsible for a significant portion of cases of male infertility, and thus commonly tested in the clinical practice, are represented by chromosomal alterations and Yq microdeletions [ 5 – 10 ]. The presence of other genetic mechanisms, such as partial Yq microdeletions [ 11 – 14 ], specific Y-chromosome haplogroups [ 15 – 18 ], and polymorphism in genes related to mitochondrial function [ 19 – 21 ] as risk factors for infertility have been suggested, but with inconclusive results. More recently, the presence of X-linked copy number variants (CNVs) in infertile males has been reported by several studies [ 22 , 23 ], but the overall incidence of these variants accounts only for a limited portion of all cases.…”

CAG-repeat polymorphisms in the polymerase γ gene and male infertility: a meta-analysis

“…(), Heidari et al . () and Poongothai ()) in and then stratified by sample size of cases, while a few surmises of possible reasons were also speculated in our article. Additionally, some mistakes in characteristic of case–control studies of Liu et al .…”