Mitochondrial DNA mutations in etiopathogenesis of male infertility

Abstract

ObjectiveTo understand role of mitochondrial (mt) mutations in genes regulating oxidative phosphorylation (OXPHOS) in pathogenesis of male infertility. Infertility affects approximately 15% of couples trying to conceive. Infertility is frequently attributed to defects of sperm motility and number. Mitochondrion and mitochondrial DNA (mtDNA) play an important role in variety of physiological process. They control the oxidative energy supply and thus are central to growth, development and differentiation. Mitochondrial function is controlled by a fine-tuned crosstalk between mtDNA and nuclear DNA (nDNA). As mitochondria supply energy by OXPHOS, any mutation in mtDNA disrupts adenosine triphosphate (ATP) production and thus result in an impaired spermatogenesis and impaired flagellar movement. As sperm midpiece has few mtDNA copies, thus enhanced number of mutant mtDNA results in early phenotypic defect which manifest as spermatogenic arrest or asthenozoospermia. Oxidative stress and mtDNA mutations are positively correlated and mutations in mitochondrial genome (mt genome) are implicated in the lowered fertilising capacity of the sperm and affects the reproductive potential of an individual.Materials and MethodsA thorough review of articles in the last 15 years was cited with reference to the below-mentioned keywords. The articles considered discuss the role of mt genome in the normal functioning of sperm and the factors associated with mt mutations and impact of these mutations on the reproductive potential.ResultsSperm motility is a very important factor for the fertilisation of ova. The energy requirements of sperm are therefore very critical for sperm. Mutations in the mitochondrial genes as COX II, ATPase 6 and 8 play an important role and disrupts ATP production affecting the spermatogenesis and sperm motility. Therefore, the aberrations in mt genome are an important etiopatholgy of male infertility.ConclusionIn the context of male infertility, mt mutations, generation of reactive oxygen species and lowered antioxidant capacity are interlinked and constitute a unified pathogenic molecular mechanism. In the era of assisted reproduction technique (ART), it is very important to distinguish between mutations in nuclear and mitochondrial genomes in sperm, as mtDNA mutations are better diagnostic and prognostic markers in infertile men opting for ART.

Forensic Relationship between ATP6 Gene and Sperm Motility in a Saudi Population

“…In the first, the amino acid changed from thrionine to isoleucine at the amino acid position 53 while in the second, the amino acid changed from leucine to phenylalanine at the position 84. In agreement with the present study, a specific point mutation at the position 9055 is correlated with small semen quality parameters in 11% of studied cases (Holyoake et al, 1999;2001;Shamsi et al, 2008). supported the role of ATP6 gene in showing significant base changes in ATP gene of infertility cases compared to the controls.…”

Loss of the Nuclear Receptor Corepressor SLIRP Compromises Male Fertility

“…It is estimated that 4% of the mouse genome encodes molecules expressed in post-meiotic male germ cells alone [5] with over 400 recombinant animal models showing alterations in fertility as a result of gene manipulation [2], [6]. Mutations in genes critical to spermatogenesis and function have been found to cause defects to functional components of sperm including mitochondria [7], [8], the acrosome [9], annulus [10] and flagellum [11].…”

Ácido Ascórbico No Diluidor Para Criopreservação De Sêmen Caprino

“…Isso acarreta uma maior quantidade de ROS na célula, consequentemente, mais danos ao DNA mitocondrial, indicando que, quanto mais células com mitocôndria sem atividade, menor a produção de ATP e fornecimento de energia para a motilidade espermática, sendo uma das possíveis causas de infertilidade em machos (24) . Por esse motivo, é importante que o acrossomo esteja íntegro, um pré-requisito essencial para a ligação do espermatozoide à zona pelúcida e para a reação acrossomal subsequente (25) .…”