Is oxidative stress an etiologic factor in idiopathic male infertility? (original) (raw)

Mystery of idiopathic male infertility: is oxidative stress an actual risk?

Fertility and Sterility, 2013

Objective: To study the role of oxidative stress in sperm dysfunction in Turkish idiopathic infertile men. Design: Prospective study. Setting: Medical laboratory. Patient(s): Semen samples from 28 idiopathic infertile men and 14 fertile men. Intervention(s): Sperm DNA fragmentation and reactive oxygen species (ROS) formation were assayed with the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) test and 2 0 ,7 0-dichlorodihydrofluorescein, respectively. Seminal plasma protein carbonyl groups (PC), nitrotyrosine (NT), malondialdehyde (MDA), and total thiol (SH) levels and ferric reducing antioxidant power (FRAP) were determined. Main Outcome Measure(s): Sperm DNA fragmentation in relation to ROS formation and seminal plasma oxidative parameters. Result(s): The number of TUNEL-positive spermatozoa from idiopathic infertile men was higher than from fertile men, and ROS formation was increased as well in infertile males. A positive correlation was detected between TUNEL-positive cells and ROS content. Seminal plasma MDA, PC, and NT levels were elevated in idiopathic infertile males. No difference was observed in the total SH content and FRAP. Seminal plasma MDA levels correlated positively with both NT and PC levels. Positive correlations were detected between DNA fragmentation and MDA, NT, and PC of seminal plasma, and between sperm ROS content and MDA levels. Conclusion(s): The results of this study support the presence of oxidative stress in sperm dysfunction in Turkish idiopathic infertile men.

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility

The World Journal of Men's Health

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective

Oxidative stress and male infertility--a clinical perspective

Human Reproduction Update, 2008

Oxidative stress occurs when the production of potentially destructive reactive oxygen species (ROS) exceeds the bodies own natural antioxidant defenses, resulting in cellular damage. Oxidative stress is a common pathology seen in approximately half of all infertile men. ROS, defined as including oxygen ions, free radicals and peroxides are generated by sperm and seminal leukocytes within semen and produce infertility by two key mechanisms. First, they damage the sperm membrane, decreasing sperm motility and its ability to fuse with the oocyte. Second, ROS can alter the sperm DNA, resulting in the passage of defective paternal DNA on to the conceptus. This review will provide an overview of oxidative biochemistry related to sperm health and will identify which men are most at risk of oxidative infertility. Finally, the review will outline methods available for diagnosing oxidative stress and the various treatments available.

Male Infertility: Pathogenetic Significance of Oxidative Stress and Antioxidant Defence (Review)

Scientific Horizons

The basis of the pathogenesis of male infertility is the processes of peroxide oxidation of biological substrates, especially lipids and proteins. By destroying the sperm membrane, toxic peroxidation products reduce its motility and ability to fertilize the egg, which is determined by a decrease in the number of motile sperm in the ejaculate. These changes lead to complete or partial male infertility. The authors of the review found that is accompanied by a damaging effect on the structural and functional activity of the gonads and is manifested, in particular, by an imbalance in the hormonal background of the male body. Similar effects are characteristic of an increase in the content of reactive Nitrogen species and its metabolites, which cause nitrosative stress, which is also the cause of male hypofertility and is inseparable from the state of oxidative stress. In scientific work it is determined that the accumulation of harmful peroxidation products leads to damage and destructi...

Relationship between oxidative stress, semen characteristics, and clinical diagnosis in men undergoing infertility investigation

To determine whether particular semen characteristics in various clinical diagnoses of infertility are associated with high oxidative stress and whether any group of infertile men is more likely to have high seminal oxidative stress. Reactive oxygen species (ROS) play an important role in sperm physiological functions, but elevated levels of ROS or oxidative stress are related to male infertility. Design: Measurement of sperm concentration, motility, morphology, seminal ROS, and total antioxidant capacity (TAC) in patients seeking infertility treatment and controls. Setting: Male infertility clinic of a tertiary care center. Patient(s): One hundred sixty-seven infertile patients and 19 controls. Intervention(s): None. Main Outcome Measure(s): Semen characteristics, seminal ROS, and TAC in samples from patients with various clinical diagnoses and controls. Result(s): Fifteen patients (9.0%) were Endtz positive and 152 (91.0%) Endtz negative. Sperm concentration, motility, and morphology were significantly reduced in all groups compared with the controls (P ϭ .02), except in varicocele associated with infection group. Mean (ϮSD) ROS levels in patient groups ranged from 2.2 Ϯ 0.13 to 3.2 Ϯ 0.35, significantly higher than controls (1.3 Ϯ 0.3; PϽ.005). Patient groups had a significantly lower mean (ϮSD) TAC from 1014.75 Ϯ 79.22 to 1173.05 Ϯ 58.07 than controls (1653 Ϯ 115.28, PϽ.001), except in the vasectomy reversal group (1532.02 Ϯ 74.24). Sperm concentration was negatively correlated with ROS both overall and within all groups (PՅ.007), with the exception of idiopathic infertility. Conclusion(s): Irrespective of the clinical diagnosis and semen characteristics, the presence of seminal oxidative stress in infertile men suggests its role in the pathophysiology of infertility. Medical or surgical treatments for infertility in these men should include strategies to reduce oxidative stress. (Fertil Steril 2000; 73:459 -64.

Oxidative stress and male infertility: a cross sectional study

Journal of the Pakistan Medical Association

Objective: To compare stress markers and antioxidants in fertile and infertile males, and to explore their effects on reproductive hormones and fertility. Methods: The cross-sectional case-control study was conducted from July 2017 to July 2018 at the Islamabad Clinic Serving Infertile Couples, Islamabad, Pakistan, and comprised male subjects aged 25-55 years. Infertile subjects were the cases, while healthy fertile males acted as the controls. Stress hormones cortisol and adrenaline and antioxidants glutathione peroxidase and superoxide dismutase were measured using enzyme-linked immunosorbent assay. Data was analysed using SPSS 22. Results: Of the 376 subjects, 241(64%) were cases and 135(36%) were controls. Median cortisol, adrenaline, superoxide dismutase and glutathione levels were significantly higher among the cases compared to te controls (p<0.05). Follicle stimulating hormone and luteinizing hormone levels were higher in cases compared to the controls (p=0.05). Mean testosterone level was higher among the controls than the cases (p<0.001). After adjusting for other covariates, every increase of 7 units in cortisol increased the prevalence of infertility by 3% (p=0.001). There was significant interaction between luteinizing hormone and testosterone in the final model (p<0.05). Conclusion: Stress together with decrease in antioxidants was found to play a significant role in reducing the fertilising potential of male infertile subjects.

Oxidative Stress and Role of Antioxidants in Male Infertility

2010

With regular cohabitation without any protection if women do not conceive for at least a period of one year is labelled as infertility. It is based on the observation that most of the normal couples achieve conception within a year of initiation of regular sex. Infertility affects approximately 15% of all couples trying to conceive. It’s a major clinical problem, affecting people medically and psychologically. Male factor infertility is the major cause in roughly half of the cases, and no identifiable cause can be found in over 25% of infertile males. Out of many causes of male infertility Oxidative stress (OS) has been attributed to affect the fertility status and thus, it has been studied extensively in recent years. Excessive production of free radicals or reactive oxygen species (ROS) can damage sperm and ROS has been extensively studied as one of the major mechanism of 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.

Impact of oxidative stress on semen parameters in normozoospermic infertile men: a case–control study

African Journal of Urology

Background Oxidative stress has been implicated in male infertility through decrease in sperm quality. However, men with normal semen parameters (normozoospermia) may be unable to fertilize their partners even when they have normal sperm function. Thus, they would be considered infertile. The purpose of this study was to investigate the role of oxidative stress in the pathogenesis of unexplained male infertility. Methods In this case–control study, infertile men with normozoospermia (n = 46) and fertile control group (n = 21) underwent seminal fluid analyses according to WHO 2010 criteria. Serum and seminal plasma levels of total antioxidant capacity (TAC), glutathione, malondialdehyde, uric acid and albumin were also measured using colorimetric methods. Results The level of total antioxidant capacity in both serum and seminal plasma was significantly lower in normozoospermic infertile men in comparison with fertile group (p

Male Infertility, Oxidative Stress and Antioxidants

Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects, 2021

Within the male reproductive system, oxidative stress (OS) has been identified as prevailing etiology of male infertility. The effects of reactive oxygen species (ROS) on male fertility depend on the dimensions, “modus operandi” of the ROS and the oxido-reduction potential (ORP) of the male reproductive tract. Hereupon, for an adequate response to OS, the cells of our body are endowed with a well-sophisticated system of defense in order to be protected. Various antioxidant enzymes and small molecular free radical scavengers, maintain the delicate balance between oxidants and reductants (antioxidants), crucial to cellular function and fertility. Therapeutic use of antioxidants is an optimal and coherent option in terms of mitigating OS and improving semen parameters. Therefore, recognizing and managing OS through either decreasing ROS levels or by increasing antioxidant force, appear to be a requesting approach in the management of male infertility. However, a clear defined attitude ...