Etiologies of sperm oxidative stress (original) (raw)
Related papers
Effect of Oxidative Stress on Sperm Cells
Glutathione System and Oxidative Stress in Health and Disease, 2020
Free radicals are unstable molecules that have an unpaired electron in their last orbital, which makes them highly unstable agents. In medicine, it has been discovered that they play an important role in cell signaling and without them some cells such as leukocytes or sperm could not perform their biological functions. To protect itself from these oxidizing agents, the cell has a defense system based on antioxidants; however, when this balance is lost and oxidizing agents exceed the cellular antioxidant capacity, the cell enters oxidative stress, which affects cellular components such as proteins, nucleic acids, lipids, amino acids, and carbohydrates, among others. In the case of spermatozoa, due to their high metabolic rate, they produce large quantities of oxygen reactive species (ROS), decreasing sperm motility, alterations in cytoplasmic components, modifications in genetic material, or sperm death. In this chapter, a review is made of a brief history of how the toxicity of oxygen and free radicals was discovered, the oxidative stress in cells, and the effect of oxidative stress in the cytoplasmic sperm membrane, in the spermatic mitochondria, in the spermatic acrosome, in the sperm DNA, and in the fertility of the female and the male.
Human Reproduction, 1998
Exposure of human spermatozoa to nicotinamide adenine dinucleotide phosphate (NADPH) resulted in the dose dependent generation of reactive oxygen species (ROS) which, at a critical level of intensity, induced lipid peroxidation, DNA damage and a dramatic decline of sperm motility. This system was then used as a model for screening the ability of different antioxidants to combat oxidative stress created through the excessive intracellular generation of toxic oxygen products of metabolism. A variety of antioxidants that has previously been shown to be protective against extracellularly derived oxidants (e.g. superoxide dismutase, catalase, vitamin E, hypotaurine) were ineffective in this system. Albumin, however, could provide complete protection against NADPH induced oxidative stress via mechanisms that did not involve the suppression of the lipid peroxidation cascade but rather the inactivation of lipid peroxides generated during this process. Albumin did not protect against DNA damage induced by NADPH but was extremely effective at preventing DNA fragmentation arising from the suppression of glutathione peroxidase activity with mercaptosuccinate. These studies emphasize that the design of clinically effective antioxidant treatments will depend, critically, upon the source of the oxidative stress. For cases involving excessive intracellular ROS generation, albumin appears to be an important means of neutralizing lipid peroxide-mediated damage to the sperm plasma membrane and DNA.
Antioxidants
This article addresses the importance of oxidative processes in both the generation of functional gametes and the aetiology of defective sperm function. Functionally, sperm capacitation is recognized as a redox-regulated process, wherein a low level of reactive oxygen species (ROS) generation is intimately involved in driving such events as the stimulation of tyrosine phosphorylation, the facilitation of cholesterol efflux and the promotion of cAMP generation. However, the continuous generation of ROS ultimately creates problems for spermatozoa because their unique physical architecture and unusual biochemical composition means that they are vulnerable to oxidative stress. As a consequence, they are heavily dependent on the antioxidant protection afforded by the fluids in the male and female reproductive tracts and, during the precarious process of insemination, seminal plasma. If this antioxidant protection should be compromised for any reason, then the spermatozoa experience patho...
Oxidative stress induced sperm DNA damage, a possible reason for male infertility
Iranian Journal of Reproductive Medicine
Background: Sperm DNA damage is an important factor in the etiology of male infertility. Objective: The aim of the study was to evaluate the association of oxidative stress induced sperm DNA damage with the pathogenesis of male infertility. Materials and Methods: The study comprised a total of 66 subjects, including fertile men (n=25) and infertile men (n=41) matched by age. Seminal malondialdehyde (MDA), phospholipid hydroperoxide (PHP), superoxide dismutase (SOD), total antioxidant status (TAS) and 8-hydroxy-2'-deoxy guanosine (8-OHdG) were estimated by spectrophotometric and ELISA based methods and the association with the sperm parameters was assessed. Results: The percentages of motile and morphologically normal cells were significantly lower (p < 0.001, p <0.001, respectivly) in infertile men. Seminal levels of MDA, PHP and 8-OHdG were significantly higher (p < 0.001, p < 0.001, and p=0. 02, respectively) while the SOD and TAS were significantly lower (p=0. 0003, p< 0.001, respectively) in infertile men. Sperm parameters were negatively correlated with MDA, PHP and 8-OHdG while positively correlated with SOD and TAS. A positive correlation of 8-OHdG with MDA and PHP and a negative correlation with TAS and SOD were also found. Conclusion: These results suggested that oxidative stress induced sperm DNA damage might have a critical effect on the etiology of infertility. Therefore, evaluation of oxidative status, antioxidant defense systems and DNA damage, together with sperm parameters might be a useful tool for diagnosis and treatment of male infertility.
The mechanisms by which Oxidative Stress and Free Radical Damage produces Male infertility
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.
Reactive Oxygen Species and Antioxidant in Seminal Plasma and Their Impact on Male Fertility
International Journal of Fertility and Sterility, 2009
Spermatozoa generate reactive oxygen species (ROS) in physiological amounts which play a role in sperm functions during sperm capacitation acrosome reaction (AR) and oocyte fusion. In addition damaged sperm are likely to be the source of ROS. The most important ROS produced by human sperm are hydrogen peroxide superoxide anion and hydroxyl radicals. Besides human seminal plasma and sperm possess an antioxidant system to scavenge ROS and prevent ROS related cellular damage. Under normal circumstances there is an appropriate balance between oxidants and antioxidants. A shift in the levels of ROS towards pro-oxidants in semen can induce oxidative stress (OS) on spermatozoa. Male infertility is associated with increased ROS and decreased total antioxidant activity in the seminal plasma. ROS induce nuclear DNA strand breaks. Besides due to a high polyunsaturated fatty acid content human sperm plasma membranes are highly sensitive to ROS induced lipid peroxidation thus decreasing membrane...
An Update on Oxidative Damage to Spermatozoa and Oocytes
BioMed Research International, 2016
On the one hand, reactive oxygen species (ROS) are mandatory mediators for essential cellular functions including the function of germ cells (oocytes and spermatozoa) and thereby the fertilization process. However, the exposure of these cells to excessive levels of oxidative stress by too high levels of ROS or too low levels of antioxidative protection will render these cells dysfunctional thereby failing the fertilization process and causing couples to be infertile. Numerous causes are responsible for the delicate bodily redox system being out of balance and causing disease and infertility. Many of these causes are modifiable such as lifestyle factors like obesity, poor nutrition, heat stress, smoking, or alcohol abuse. Possible correctable measures include foremost lifestyle changes, but also supplementation with antioxidants to scavenge excessive ROS. However, this should only be done after careful examination of the patient and establishment of the individual bodily antioxidant needs. In addition, other corrective measures include sperm separation for assisted reproductive techniques. However, these techniques have to be carried out very carefully as they, if applied wrongly, bear risks of generating ROS damaging the germ cells and preventing fertilization.
Increase of oxidative stress in human sperm with lower motility
Fertility and Sterility, 2008
Objective: To investigate the causal role of oxidative-stress status on human sperm motility. Design: To demonstrate that sperm with higher oxidative damage have a lower antioxidant capacity. Setting: University hospital infertility center. Patient(s): Seventy-eight semen samples were obtained from 35 healthy donors who had normal semen characteristics and from 43 infertile or subfertile males. Intervention(s): The levels of oxidative damage (8-hydroxy-2 0 -deoxyguanosine [8-OHdG] and lipid peroxides) and antioxidants (retinol, a-tocopherol, ascorbate, and protein thiols) in the spermatozoa and/or seminal plasma were measured. Main Outcome Measure(s): We analyzed the specific content of 8-OHdG and lipid peroxides by using highperformance liquid chromatography (HPLC)-electrochemical detection and HPLC-fluorescence analysis, respectively. Retinol and a-tocopherol were analyzed by using an HPLC system, whereas ascorbate and protein thiols were determined by using spectrophotometry. 8-Hydroxy-2 0 -deoxyguanosine was visualized by immunofluorescent staining with an anti-8-OHdG antibody that was conjugated with fluorescein isothiocyanate conjugate. Lipid peroxides in spermatozoa were stained with a fluorescent dye, C11-BODIPY 581/591 . Result(s): Statistically significant negative correlations were revealed between sperm motility and 8-OHdG and between motility and lipid peroxides. Statistically significant positive correlations were found between sperm motility and the levels of retinol, a-tocopherol, ascorbate, and protein thiols of seminal plasma. 8-Hydroxy-2 0 -deoxyguanosine and lipid peroxides in spermatozoa were found to be present mostly in mitochondria. Conclusion(s): Oxidative stress and oxidative damage were increased significantly in spermatozoa with declined motility, and the antioxidant capacities in the spermatozoa and seminal plasma were lower in males who had infertility or subfertility.
Oxidative Damage to Sperm DNA: Clinical Implications
Andrology
Background: Sperm DNA is susceptible to oxidative damage due to intrinsic and extrinsic factors which cause oxidative stress and due to limited DNA damage detection and repair mechanism. Reactive oxygen species (ROS) are the chief cause of sperm DNA damage. So, this study was planned to assess oxidative stress levels and correlate with sperm DNA damage. Material and Method: The study included 35 men who had fathered a child in the last one year and 54 male partners of couple experiencing primary infertility. Semen analysis was done according to World Health Organization (1999) criteria. ROS measurement was done by direct chemiluminescence method using luminol as a probe. DNA damage was assessed by sperm chromatin structure assay (SCSA) and expressed as percentage DFI. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) estimation was carried out by competitive ELISA. Results: The seminal ROS level (RLU/sec/million sperm) was significantly higher (40.52 ± 18.32) in infertile men as compared to ...