Oxidative Stress, Testicular Inflammatory Pathways and Male Reproduction (original) (raw)
Related papers
Role of oxidative stress, infection and inflammation in male infertility
Andrologia, 2018
Oxidative stress (OS), defined as an overabundance of reactive oxygen species (ROS) or a deficiency of antioxidants, has been linked to sperm damage and male infertility. There are many sources of OS and inflammation including varicocele, tobacco usage, alcohol, obesity/metabolic syndrome, leukocytospermia, sexually transmitted disease (i.e., Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum), bacterial prostatitis, microorganism mutations leading to more OS, and viral infections (i.e., human immunodeficiency virus, hepatitis). This review is focusing on infection and inflammation-mediated OS, the inflammatory markers underlying pathology, clinical significance in male infertility, and a brief description of the recommended treatment modalities.
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.
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.
Is oxidative stress an etiologic factor in idiopathic male infertility?
2000
Aim: The total antioxidant capacity (TAC) and total peroxide (TP) levels in the blood and seminal plasma of idiopathic infertile patients were compared with those of fertile controls to determine the role of oxidative stress in the etiology of idiopathic male infertility. Material and methods: Thirty-two idiopathic infertile males and 30 healthy, married, age-matched control subjects were included in the
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 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.
Journal of Personalized Medicine
Oxidative and inflammatory damage underlie several conditions related to male infertility, including varicocele. Free light chains of immunoglobulins (FLCs) are considered markers of low-grade inflammation in numerous diseases. Coenzyme Q10 (CoQ10), a lipidic antioxidant and anti-inflammatory compound, is involved in spermatozoa energy metabolism and motility. We aimed to evaluate FLCs’ seminal levels in patients with varicocele in comparison to control subjects and to correlate them with CoQ10 and Total Antioxidant Capacity (TAC) in human semen. Sixty-five patients were enrolled. Semen analysis was performed; patients were divided into three groups: controls, 12 normozoospermic patients, aged 34 (33–41) years; varicocele (VAR), 29 patients, aged 33 (26–37) years; and idiopathic, 24 oligo-, astheno- and oligoasthenozoospermic patients aged 37 (33.5–40.5) years. FLCs (κ and λ) were assayed by turbidimetric method; CoQ10 by HPLC; TAC by spectrophotometric method. λ FLCs showed a trend...
Impact of Inflammation on Male Reproductive Tract
Fertility in the male is dependent on the proper production of sperm cells. This process , called spermatogenesis is very complex and involves the synchronization of numerous factors. The presence of pro–inflammatory cytokines, tumor necrosis factor alpha (TNF–α), interleukin–1 alpha (IL–1 α) and interleukin 1 beta (IL–1 β) cy-tokines in the male reproductive tract (testis, epididymis and sperm) may have certain physiological functions. However, when the levels of these cytokines are higher than normal, as seen in conditions of inflammation, they become very harmful to sperm production. Moreover, inflammation is also associated with oxidative stress and the latter is well known to impair sperm function. Epidemiological studies regarding male infertility have revealed that more and more infertile men suffer from acute or chronic inflammation of the genitourinary tract, which often occurs without any symptoms. The inflammatory reactions within the male genital tract are inevitably connected with oxidative stress. Oxidative stress, especially in sperm, is harmful because it damages sperm DNA and causes apoptosis in sperm. This article reviewed the suggested mechanisms and contribution of inflammation to male infertility. In addition, the review was further strengthened by discussing how inflammation affects both fertility and assisted reproductive technologies (ART).
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...
Oxidative Stress and Male Infertility: Evidence From a Research Perspective
Frontiers in Reproductive Health, 2022
Male fertility potential can be influenced by a variety of conditions that frequently coincide. Spermatozoa are particularly susceptible to oxidative damage due to their limited antioxidant capacity and cell membrane rich in polyunsaturated fatty acids (PUFAs). The role of oxidative stress (OS) in the etiology of male infertility has been the primary focus of our Stellenbosch University Reproductive Research Group (SURRG) over the last 10 years. This review aims to provide a novel insight into the impact of OS on spermatozoa and male reproductive function by reviewing the OS-related findings from a wide variety of studies conducted in our laboratory, along with those emerging from other investigators. We will provide a concise overview of the production of reactive oxygen species (ROS) and the development of OS in the male reproductive tract along with the physiological and pathological effects thereof on male reproductive functions. Recent advances in methods and techniques used fo...