The mechanisms by which Oxidative Stress and Free Radical Damage produces Male infertility (original) (raw)

In a healthy body, ROS (reactive oxygen species) and antioxidants remain in balance. When the balance is disrupted towards an overabundance of ROS, oxidative stress (OS) occurs. OS results from an imbalance between prooxidants (free radical species) and the body's scavenging ability (antioxidants). ROS are a double-edged swordthey serve as key signal molecules in physiological processes but also have a role in pathological processes. The production of ROS is a normal physiological event in various organs including the testis. Overproduction of ROS can be detrimental to sperm and being associated with male infertilities. The excessive generation of ROS by abnormal spermatozoa, contaminating leukocytes and by a various type of pollutants has been identified as detrimental etiologies for male infertilities Free radicals are substances with one or more unpaired electrons, which are formed as a results of many physiological and pathological cellular metabolic processes, especially in mitochondria. Enzymatic (Catalase, superoxide dismutase) and non enzymatic (vitamins A and E) natural antioxidant defense mechanisms exist; however, these mechanisms may be overcome, causing lipid peroxidation to take place. For example, breakdown in the cells results in the formation of molecules whose further metabolism in the cell leads to ROS production. Thus increased OS stimulates the activity of enzymes called cytochrome P450, which contribute to ROS production. . Oxidative stress index (OSI) was calculated as ([TOS/TAS] x 100). TOS and OSI were significantly higher and PON-1 activity and TAS were significantly lower in subfertile male with abnormal semen parameters than in male with idiopathic subfertility and fertile donors. PON-1 activity was also strongly correlated with sperm concentration, motility, and morphology in the overall group. The receiver operating characteristic curve analysis revealed a high diagnostic value for PON-1 activity with respect to male-factor sub fertility. ROS may cause infertility by two principal mechanisms, first ROS damage the sperm membrane which in turn reduces the sperm motility and ability to fuse with the oocyte secondly, and ROS directly damage sperm DNA, compromising the paternal genomic contribution to the embryo. Oxidative stress due to excessive production of ROS, impaired antioxidant defense mechanisms, or both precipitates a range of pathologies that are currently believed to negatively affect the male reproductive function. Oxidative stress-induced damage to sperm may be mediated by lipid peroxidation of the sperm plasma membrane, reduction of sperm motility, and damage to the DNA in the sperm nucleus, as the production of ROS is one of the principal mechanisms by which neutrophils destroy pathogens, it is not surprising that seminal leukocytes have the potential to cause oxidative stress. Despite the established role of OS in the pathogenesis of male infertility, there is a lack of consensus as to the clinical utility of seminal OS testing in an infertility clinic. One important reason for the inability to utilize the OS test in clinical practice is related to the lack of a standard protocol for assessment of seminal OS. Antioxidants are powerful and there are few trials investigating antioxidant supplementation in male reproduction. Several researches indicate that the diagnostic and prognostic capabilities of the seminal OS test are beyond those of conventional tests of sperm quality and function. The OS test can accurately discriminate between fertile and infertile male and identify male with a clinical diagnosis of male-factor infertility that are likely to initiate a pregnancy when followed over a period of time. We strongly believe that incorporating such a test into the routine andrology workup is an important step for the future of the male infertility practice. The resulting state of the cell, known as (OS) can lead to cell injury. ROS production and Lipid peroxidation, free radical and oxidative stress in relation to fertility are the aim of this review [Magda M El-Tohamy. The mechanisms by which Oxidative Stress and Free Radical Damage produces Male infertility.