Role of reactive oxygen species in the pathogenesis of mitochondrial DNA (mtDNA) mutations in male infertility.
Infertility affects about 15 per cent married couples half of which may be attributed to men with low sperm motility (asthenozoospermia), low sperm count (oligozoospermia) or abnormal sperm morphology (teratozoospermia). As mitochondria are the energy source for initiation, differentiation and function of the germ cells, mutation in mitochondrial genome can impair the formation of mature spermatozoa. Mutations in mitochondrial genome are identified in patients with fertility problems. However, mitochondria are also both the source and target of reactive oxygen species (ROS). ROS are normally generated at low levels by human spermatozoa in order to perform its physiological function. However, if the generation of these reactive free radicals overwhelm the antioxidant defense system, this can lead to oxidative stress, which is characterized by mitochondrial and nuclear genome damage. So both ROS and mtDNA mutations are considered to be the major aetiological factors in a variety of human diseases including male infertility. Identification of novel mutations in mtDNA of infertile patients with supraphysiological levels of ROS are considered to be important to gain better understanding of the aetiology of idiopathic infertility. Early detection and prompt antioxidant therapy can prevent ROS induced DNA damage. This has far reaching impact if such men opt for assisted reproductive technology (ART)/in vitro fertilization.
Venkatesh
S
S
Laboratory for Molecular Reproduction & Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi , India.
Deecaraman
M
M
Kumar
R
R
Shamsi
M B
MB
Dada
R
R
D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species