scholarly journals Redox Balance in Male Infertility: Excellence through Moderation—“Μέτρον ἄριστον”

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1534
Author(s):  
Evangelos N. Symeonidis ◽  
Evangelini Evgeni ◽  
Vasileios Palapelas ◽  
Dimitra Koumasi ◽  
Nikolaos Pyrgidis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Male Infertility ◽  
Medical Condition ◽  
Wide Spectrum ◽  
Semen Analysis ◽  
Redox Balance ◽  
Male Reproduction ◽  
Specific Patient ◽  
Reductive Stress ◽  
The Impact

Male infertility, a relatively common and multifactorial medical condition, affects approximately 15% of couples globally. Based on WHO estimates, a staggering 190 million people struggle with this health condition, and male factor is the sole or contributing factor in roughly 20–50% of these cases. Nowadays, urologists are confronted with a wide spectrum of conditions ranging from the typical infertile male to more complex cases of either unexplained or idiopathic male infertility, requiring a specific patient-tailored diagnostic approach and management. Strikingly enough, no identifiable cause in routine workup can be found in 30% to 50% of infertile males. The medical term male oxidative stress infertility (MOSI) was recently coined to describe infertile men with abnormal sperm parameters and oxidative stress (OS), including those previously classified as having idiopathic infertility. OS is a critical component of male infertility, entailing an imbalance between reactive oxygen species (ROS) and antioxidants. ROS abundance has been implicated in sperm abnormalities, while the exact impact on fertilization and pregnancy has long been a subject of considerable debate. In an attempt to counteract the deleterious effects of OS, urologists resorted to antioxidant supplementation. Mounting evidence indicates that indiscriminate consumption of antioxidants has led in some cases to sperm cell damage through a reductive-stress-induced state. The “antioxidant paradox”, one of the biggest andrological challenges, remains a lurking danger that needs to be carefully avoided and thoroughly investigated. For that reason, oxidation-reduction potential (ORP) emerged as a viable ancillary tool to basic semen analysis, measuring the overall balance between oxidants and antioxidants (reductants). A novel biomarker, the Male infertility Oxidative System (MiOXSYS®), is a paradigm shift towards that goal, offering a quantification of OS via a quick, reliable, and reproducible measurement of the ORP. Moderation or “Μέτρον” according to the ancient Greeks is the key to successfully safeguarding redox balance, with MiOXSYS® earnestly claiming its position as a guarantor of homeostasis in the intracellular redox milieu. In the present paper, we aim to offer a narrative summary of evidence relevant to redox regulation in male reproduction, analyze the impact of OS and reductive stress on sperm function, and shed light on the “antioxidant paradox” phenomenon. Finally, we examine the most up-to-date scientific literature regarding ORP and its measurement by the recently developed MiOXSYS® assay.

scholarly journals Oxidative Stress, Testicular Inflammatory Pathways and Male Reproduction

2021 ◽  
Vol 22 (18) ◽  
pp. 10043
Author(s):  
Sulagna Dutta ◽  
Pallav Sengupta ◽  
Petr Slama ◽  
Shubhadeep Roychoudhury
Keyword(s):  
Oxidative Stress ◽  
Male Infertility ◽  
Reproductive Tract ◽  
Inflammatory Responses ◽  
Male Reproduction ◽  
Male Reproductive Tract ◽  
Proinflammatory Mediators ◽  
Global Issue ◽  
Causative Factors ◽  
Infertility Patients

Inflammation is among the core causatives of male infertility. Despite male infertility being a serious global issue, “bits and pieces” of its complex etiopathology still remain missing. During inflammation, levels of proinflammatory mediators in the male reproductive tract are greater than usual. According to epidemiological research, in numerous cases of male infertility, patients suffer from acute or chronic inflammation of the genitourinary tract which typically occurs without symptoms. Inflammatory responses in the male genital system are inextricably linked to oxidative stress (OS). OS is detrimental to male fertility parameters as it causes oxidative damage to reproductive cells and intracellular components. Multifarious male infertility causative factors pave the way for impairing male reproductive functions via the common mechanisms of OS and inflammation, both of which are interlinked pathophysiological processes, and the occurrence of any one of them induces the other. Both processes may be simultaneously found in the pathogenesis of male infertility. Thus, the present article aims to explain the role of inflammation and OS in male infertility in detail, as well as to show the mechanistic pathways that link causative factors of male reproductive tract inflammation, OS induction, and oxidant-sensitive cellular cascades leading to male infertility.

scholarly journals Restoring redox balance enhances contractility in heart trabeculae from type 2 diabetic rats exposed to high glucose

2015 ◽  
Vol 308 (4) ◽  
pp. H291-H302 ◽  
Author(s):  
Niraj M. Bhatt ◽  
Miguel A. Aon ◽  
Carlo G. Tocchetti ◽  
Xiaoxu Shen ◽  
Swati Dey ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Negative Impact ◽  
Antioxidant Activities ◽  
Contractile Function ◽  
Heart Function ◽  
Redox Balance ◽  
The Impact ◽  
Type 2 Diabetic

Hearts from type 2 diabetic (T2DM) subjects are chronically subjected to hyperglycemia and hyperlipidemia, both thought to contribute to oxidizing conditions and contractile dysfunction. How redox alterations and contractility interrelate, ultimately diminishing T2DM heart function, remains poorly understood. Herein we tested whether the fatty acid palmitate (Palm), in addition to its energetic contribution, rescues function by improving redox [glutathione (GSH), NAD(P)H, less oxidative stress] in T2DM rat heart trabeculae subjected to high glucose. Using cardiac trabeculae from Zucker Diabetic Fatty (ZDF) rats, we assessed the impact of low glucose (EG) and high glucose (HG), in absence or presence of Palm or insulin, on force development, energetics, and redox responses. We found that in EG ZDF and lean trabeculae displayed similar contractile work, yield of contractile work (Ycw), representing the ratio of force time integral over rate of O2 consumption. Conversely, HG had a negative impact on Ycw, whereas Palm, but not insulin, completely prevented contractile loss. This effect was associated with higher GSH, less oxidative stress, and augmented matrix GSH/thioredoxin (Trx) in ZDF mitochondria. Restoration of myocardial redox with GSH ethyl ester also rescued ZDF contractile function in HG, independently from Palm. These results support the idea that maintained redox balance, via increased GSH and Trx antioxidant activities to resist oxidative stress, is an essential protective response of the diabetic heart to keep contractile function.

scholarly journals Epigenetics in Male Infertility

2021 ◽  
Author(s):  
Hayfa H. Hassani ◽  
Rakad M. Kh AL-Jumaily ◽  
Fadhel M. Lafta
Keyword(s):  
Gene Expression ◽  
Male Infertility ◽  
Medical Condition ◽  
Wide Spectrum ◽  
Regulatory Elements ◽  
Great Promise ◽  
Genomic Integrity ◽  
Idiopathic Male Infertility ◽  
Scientific Attention ◽  
Proteomic Research

Male infertility is a complex medical condition, in which epigenetic factors play an important role. Epigenetics has recently gained significant scientific attention since it has added a new dimension to genomic and proteomic research. As a mechanism for maintaining genomic integrity and controlling gene expression, epigenetic modifications hold a great promise in capturing the subtle, yet very important, regulatory elements that might drive normal and abnormal sperm functions. The sperm’s epigenome is known to be marked by constant changing over spermatogenesis, which is highly susceptible to be influenced by a wide spectrum of environmental stimuli. Recently, epigenetic aberrations have been recognized as one of the causes of idiopathic male infertility. Recent advances in technology have enabled humans to study epigenetics role in male infertility.

scholarly journals Chitosan/Selenium Nanoparticles Attenuate Diclofenac Sodium-Induced Testicular Toxicity in Male Rats

Crystals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1477
Author(s):  
Samy M. El-Megharbel ◽  
Fawziah A. Al-Salmi ◽  
Sarah Al-Harthi ◽  
Khadeejah Alsolami ◽  
Reham Z. Hamza
Keyword(s):  
Oxidative Stress ◽  
Diclofenac Sodium ◽  
Chitosan Nanoparticles ◽  
Reproductive Toxicity ◽  
Male Reproduction ◽  
Male Rats ◽  
Antioxidant Enzyme Activities ◽  
Testicular Function ◽  
Wide Range ◽  
The Impact

The detrimental effect of diclofenac sodium (Diclo-Na) on male reproductive organs is reported upon in this paper. Chitosan is a polysaccharide composed of various amounts of glucosamine. Chitosan nanoparticles (CH-NPs) have attracted much attention owing to their biomedical activity. Selenium (Se) has a vital role in nutrition, plays an important role in enhancing male reproduction, and has a wide range of free radical scavenging activities. However, the study of the impact of chitosan nanoparticles in combination with Se (IV) (CH-NPs/Se) on male reproductive toxicity associated with Diclo-Na administration is lacking in recent literature. The current study assessed the ameliorative effects of complexes of CH-NPs/Se (IV) on Diclo-Na and the ways in which they alter reproductive toxicity in male rats. Male rats were treated for 30 days successively, either with Diclo-Na (10 mg/kg) or co-treated with a CH-NPs/Se complex (280 mg/kg). Sperm characteristics, marker enzymes of testicular function, LH, FSH, and testosterone were evaluated in addition to oxidative stress markers and histological alterations. CH-NPs/Se significantly alleviated Diclo-Na-induced decline in sperm count and motility, testicular function enzymes, and levels of LH and testosterone in serum. Additionally, CH-NPs/Se co-administration at 280 mg/Kg, inhibited the Diclo-Na-induced decline of antioxidant enzyme activities and elevated oxidative stress indices and reactive free radicals in testicular homogenates of male rats. CH-NPs/Se (280 mg/kg) alone improved Diclo-Na and ameliorated histological damages in exposed rats. In conclusion, chitosan improved testicular function in Diclo-Na-treated rats by enhancing the testosterone hormone levels, ameliorating testicular tissue, and inhibiting markers of oxidative stress in male rats.

scholarly journals Oxidative Stress and Reproductive Function in the Aging Male

Biology ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 282
Author(s):  
Paulina Nguyen-Powanda ◽  
Bernard Robaire
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Defense ◽  
Structural Integrity ◽  
Germ Line ◽  
Reproductive Function ◽  
Antioxidant Defense System ◽  
Male Reproduction ◽  
Paternal Age ◽  
Theories Of Aging ◽  
The Impact

With the delay of parenthood becoming more common, the age at which men father children is on the rise. While the effects of advanced maternal age have been well documented, only recently have studies started to focus on the impact of advanced paternal age (APA) in the context of male reproduction. As men age, the antioxidant defense system gradually becomes less efficient and elevated levels of reactive oxygen species (ROS) accumulate in spermatozoa; this can impair their functional and structural integrity. In this review, we present an overview of how oxidative stress is implicated in male reproductive aging by providing a summary of the sources and roles of ROS, the theories of aging, and the current animal and human studies that demonstrate the impacts of APA on the male germ line, the health of progeny and fertility, and how treatment with antioxidants may reverse these effects.

O-040 The evolution of WHO Manual. Where are we now?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
S Esteves
Keyword(s):  
Reproductive Health ◽  
Male Infertility ◽  
Reference Values ◽  
Semen Analysis ◽  
Well Being ◽  
World Health ◽  
Reference Ranges ◽  
Human Semen ◽  
The Impact ◽  
Lower Limits

Abstract text Male factor infertility is associated with impaired overall health, decreased life expectancy, lower quality of life and may affect reproductive outcomes even under assisted reproductive technology (ART) settings. Male factors, alone or combined with female factors, contribute to at least 50% of reported infertility cases. Despite this, the male partner is often overlooked in the evaluation and treatment of infertility. A routine semen analysis is frequently the only test carried out to assess a man’s fertility potential. The state-of-art on how the human semen should be assessed is provided by the World Health Organization (WHO), which periodically releases manuals that include specific protocols and reference standards. These manuals include detailed laboratory methods for semen examination, protocols for sperm preparation and cryopreservation, quality assurance and quality control, results’ interpretation, and reference ranges. Unlike the previous four versions, the latest 2010 WHO reference values relied on clinical chemistry principles to generate 95% intervals for sperm volume, count, motility, vitality, and morphology from recent fathers. The fifth centile was deemed suitable for representing semen characteristics at lower limits. The reference values ultimately obtained were markedly lower than those previously reported, raising concerns about its clinical utility and generalizability. Criticisms included the limited geographical area of patients analyzed, the methods used for semen evaluation, and the potential impact of the new reference range on patient referral, diagnosis, and treatment guidance. An updated new WHO manual (6th edition) is about to be released with much expectation. Although semen analysis remains one of the cornerstones of the infertility evaluation, a male infertility workup primarily based on routine semen analysis does not provide men with an optimal fertility pathway for many reasons. First, reference intervals do not reliably distinguish fertile from subfertile subjects. Second, an individual patient’s results have limited prognostic value for both natural and assisted conception unless at extreme lower limits. Third, there is a wide variation in how laboratories perform a semen analysis. Lastly, routine semen analysis does not detect sperm DNA defects that might adversely impact embryo development, implantation, and offspring’s health. Guidelines issued by professional societies recommend that a full andrological assessment be performed in all men with couple infertility. Well-trained reproductive urologists or clinical andrologists should perform the male evaluation, including a detailed history, physical examination, semen analysis, endocrine assessment, and other tests as needed. Therefore, the importance of WHO manuals remains critical. However, the goals of a comprehensive male infertility workup go beyond the laboratory assessment of human semen. It comprises i. Diagnosis, i.e., detection of any underlying relevant medical or lifestyle conditions potentially impairing the (reproductive) health of the male or his offspring; ii. Counselling, particularly regarding the impact of infertility, genetic factors, age, and lifestyle on pregnancy prospects, reproductive and overall health, and offspring’s well-being; and iii. Management Guidance, i.e., identifying optimal treatment options to improve the likelihood of achieving natural pregnancy or ART success. The prevention and management of male infertility are integral components of comprehensive sexual and reproductive health services needed to attain a sustainable development goal.

scholarly journals Experimental Guidelines for Studies Designed to Investigate the Impact of Antioxidant Supplementation on Exercise Performance

2010 ◽  
Vol 20 (1) ◽  
pp. 2-14 ◽  
Author(s):  
Scott K. Powers ◽  
Ashley J. Smuder ◽  
Andreas N. Kavazis ◽  
Matthew B. Hudson
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Antioxidant Capacity ◽  
Exercise Performance ◽  
Human Performance ◽  
Experimental Situation ◽  
Redox Balance ◽  
Experimental Conditions ◽  
Wide Range ◽  
The Impact

Research interest in the effects of antioxidants on exercise-induced oxidative stress and human performance continues to grow as new scientists enter this field. Consequently, there is a need to establish an acceptable set of criteria for monitoring antioxidant capacity and oxidative damage in tissues. Numerous reports have described a wide range of assays to detect both antioxidant capacity and oxidative damage to biomolecules, but many techniques are not appropriate in all experimental conditions. Here, the authors present guidelines for selecting and interpreting methods that can be used by scientists to investigate the impact of antioxidants on both exercise performance and the redox status of tissues. Moreover, these guidelines will be useful for reviewers who are assigned the task of evaluating studies on this topic. The set of guidelines contained in this report is not designed to be a strict set of rules, because often the appropriate procedures depend on the question being addressed and the experimental model. Furthermore, because no individual assay is guaranteed to be the most appropriate in every experimental situation, the authors strongly recommend using multiple assays to verify a change in biomarkers of oxidative stress or redox balance.

scholarly journals Male fertility: review of the publications of July - September 2020

2020 ◽  
Vol 8 (4) ◽  
pp. 122-128
Author(s):  
D. S. Rogozin
Keyword(s):  
Male Infertility ◽  
Reproductive System ◽  
Male Fertility ◽  
Selection Criteria ◽  
Redox Balance ◽  
Paternal Age ◽  
Practical Significance ◽  
The Third ◽  
The Impact ◽  
Scimago Journal Rank

The article provides an overview of the most significant publications on the male infertility topic. The main selection criteria were considered the practical significance of the article, as well as the impact factor of the journal in which it was published, according to the SCImago Journal Rank (SJR). As a result, a list of 10 works published in the third quarter (July - September) of 2020 was formed. The review included articles on the following issues: redox balance in the male reproductive system, advanced paternal age, the effect of a new nasal form of testosterone on fertility, the correlation of PSA levels with infertility, as well as new data on the effect of COVID-19 on male fertility.

Administration of Antioxidants in the Infertile Male: When it may have a Beneficial Effect?.

2020 ◽  
Vol 26 ◽  
Author(s):  
Zsolt Kopa ◽  
Marton Keszthelyi ◽  
Nikolaos Sofikitis
Keyword(s):  
Oxidative Stress ◽  
Male Infertility ◽  
Membrane Damage ◽  
Live Birth Rate ◽  
Redox Status ◽  
Antioxidant Systems ◽  
Sperm Function ◽  
Antioxidant Treatment ◽  
Reductive Stress ◽  
Pre Treatment

Background: Reactive Oxygen Species (ROS) are required for intact spermatogenesis and sperm function, but excessive levels will cause oxidative stress, impairing sperms and sperm function due to membrane damage and DNA fragmentation. Objective: Theoretically, antioxidant supplementation may act as a protecting system against free radicals. Since infertile males have higher levels of ROS, nutritional supplements are widely used for protecting sperms. In the recent review authors summarize the most recent data regarding the effect of antioxidant treatment and draw an attention of the limitations of antioxidant use in male infertility. Methods: The recent review gives an update of antioxidant treatment in male infertility. Results: Improvement of sperm parameters was reported in the majority of studies. Comparing different antioxidants versus placebo showed low certainty of evidence with a serious risk of bias, and there is a lack regarding certain doses, pregnancy rate, and live birth rate outcomes. Various clinical studies and randomized control trials reported even negative outcomes. Conflicting findings lead the attention to the study of biochemical features of the oxidant vs. antioxidant equilibrium. Higher exposure to antioxidants will result in „reductive stress”, which has harmful effects on sperm function, moreover can negatively influence embryo development. Reductive stress is as dangerous as oxidative stress and may act as a cause of different human pathologies. Conclusion: An intact balance of oxidant and antioxidant systems is required to normal sperm function. No guideline exists for the antioxidant dose regimen and treatment duration. Overdosing can result in reductive stress, which is also harmful to fertility and can cause several diseases. Assessment of the pre-treatment redox status can be recommended before the administration of exogenous antioxidants.

A Novel Notch/NRF2 Mechanism Mediates Reductive Stress in Acute Myeloblastic Leukemia (AML): A Therapeutic Strategy to Overcome Chemoresistance

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4834-4834 ◽  
Author(s):  
Sankaranarayanan Kannan ◽  
Patrick A. Zweidler-McKay
Keyword(s):  
Oxidative Stress ◽  
Conflicts Of Interest ◽  
Notch Pathway ◽  
Redox Balance ◽  
Antioxidant Response ◽  
Protective Mechanism ◽  
Master Regulator ◽  
Metabolite Formation ◽  
Reductive Stress ◽  
Notch Activation

Abstract Background: Chronic oxidative stress (COS) is the consequence of prolonged elevation of reactive oxygen species (ROS). In the context of AML, COS leads to sustained induction of antioxidant pathways to compensate for COS. The presence of abundant antioxidants may contribute to chemoresistance in AML. NRF2 is a master regulator of the antioxidant response, is induced by oxidative stress and functions as a cyto-protective mechanism in acute oxidative stress. In AML, sustained NRF2-activation can be viewed as a pathological maladaptation as it leads to elevated reductive metabolite formation, termed reductive stress (RS). In this study we describe a novel link between NRF2-induced reductive stress and the Notch pathway in AML. Approach: Redox balance was measured in AML patient samples in the setting of Notch activation (via DLL1 ligand) and/or NRF2 inhibition (via Brusatol). Results: AML samples demonstrate increased reductive metabolites (i.e. reductive stress) compared to controls and Notch activation decreases aberrant reductive metabolite levels to control baseline (GSH/GSSG ratio, panel A). Mechanistically, Notch signaling induced increased ROS formation, decreased NRF2 protein levels, and decreased expression of multiple NRF2-responsive antioxidants (data not shown). Importantly, Notch activation also enhanced the efficacy of an NRF2 inhibitor Brusatol (from *P≤0.05 to **P≤0.01) in combination with ROS-producing chemotherapeutic doxorubicin, eradicating >98% of AML cells within 48 hours (** P≤0.01; panel B). Conclusions: We describe the aberrant accumulation of reductive metabolites in human AML as a potential cytoprotective maladaptation, i.e. reductive stress. Furthermore, we demonstrate a novel mechanism whereby Notch activation regulates the antioxidant response via suppression of the master regulator NRF2. These data establish the pivotal role of Notch/NRF2 in the regulation of antioxidant responses in AML, which have potential clinical significance for ROS-inducing chemotherapies. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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