A novel m.6307A>G mutation in the mitochondrialCOXIgene in asthenozoospermic infertile men

Abstract

Infertility affects 10-15% of the population, of which approximately 40% is due to male etiology and consists primarily of low sperm count (oligozoospermia) and/or abnormal sperm motility (asthenozoospermia). Recently, it has been demonstrated that mtDNA substitutions can influence semen quality. In this study, we performed a sequence analysis of the mitochondrial cytochrome oxidase I (COXI) gene in 31 infertile men suffering from asthenozoospermia in comparison to 33 normozoospermic infertile men and 100 fertile men from the Tunisian population. A novel m.6307A>G mutation was found in sperm mitochondrial DNA (mtDNA). This mutation was found in six asthenozoospermic patients, and was absent in normozoospermic and fertile men. We also detected 21 known substitutions previously reported in the Human Mitochondrial Database. The m.6307A>G mutation substitutes a highly conserved asparagine at position 135 to serine. In addition, PolyPhen-2 analysis predicted that this variant is "probably damaging.

MiR-125b-2 Knockout in Testis Are Associated with Targeting to PAP Gene, Mitochondrial Copy Number and Impaired Sperm Quality

“…Infertility is a common human health problem [1] and 40%-50% of all cases are due to male deficiency. In recent years, several clinical studies [2,3] have shown that sperm quality and impaired spermatogenesis can cause male infertility. The process of spermatogenesis is highly sensitive to fluctuations in the environment and involves numerous endocrine and paracrine signals to coordinate the self-renewal and differentiation of spermatogonial stem cells [4].…”

Mitochondrial DNA sequencing and large-scale genotyping identifies MT-ND4 gene mutation m.11696G>A associated with idiopathic oligoasthenospermia

“…The role of mitochondria in spermatogenesis has been extensively researched [ 17 , 18 ]. However, former studies paid close attention to single or specific genetic variants of mitochondrial genes participated in spermatogenesis [ 19 , 20 ]. To systematically explore the role of whole mtDNA genome on spermatogenesis, NGS was applied in 233 idiopathic oligoasthenospermia cases and 233 healthy controls, and susceptible genetic variants were evaluated with SNPscan in 670 cases and 793 controls.…”

‘Infertile’ studies on mitochondrial DNA variation in asthenozoospermic Tunisian men

“…We reviewed five articles published by the same research group from Tunisia. These articles were published in 2012 [27] , 2013 [10] , [11] , and 2014 [12] , [16] . Note that one of the 2014 papers [16] was indexed in PubMed using the first names of the authors instead of the family names, but the authors are virtually the same and following the same order in the five publications.…”

“…During the last few decades, variation in the mitochondrial DNA (mtDNA) molecule has been studied in the context of many complex multifactorial diseases [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] . In this regard, the search for mtDNA variation related to infertility has also received the attention of a vast body of literature [10] , [11] , [12] , [13] , [14] , [15] , [16] , [36] . Some of the positive findings were critically questioned by others [13] , [17] , who pointed out problems of different nature, including methodological and theoretical misconceptions, as well as important statistical deficiencies [7] , [18] , [19] , [20] , [21] .…”