scholarly journals Antioxidant Paradox in Male Infertility: ‘A Blind Eye’ on Inflammation

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 167
Author(s):  
Sulagna Dutta ◽  
Pallav Sengupta ◽  
Shubhadeep Roychoudhury ◽  
Srikumar Chakravarthi ◽  
Chee Woon Wang ◽  
...  
Keyword(s):  
Male Infertility ◽  
Redox Homeostasis ◽  
Male Reproduction ◽  
Cellular Damage ◽  
Normal Male ◽  
Reproductive Tissues ◽  
Reductive Stress ◽  
Endogenous Antioxidant ◽  
And Oxidative Stress ◽  
Selection Of

The pathophysiology of male infertility involves various interlinked endogenous pathways. About 50% of the cases of infertility in men are idiopathic, and oxidative stress (OS) reportedly serves as a central mechanism in impairing male fertility parameters. The endogenous antioxidant system operates to conserve the seminal redox homeostasis required for normal male reproduction. OS strikes when a generation of seminal reactive oxygen species (ROS) overwhelms endogenous antioxidant capacity. Thus, antioxidant treatment finds remarkable relevance in the case of idiopathic male infertility or subfertility. However, due to lack of proper detection of OS in male infertility, use of antioxidant(s) in some cases may be arbitrary or lead to overuse and induction of ‘reductive stress’. Moreover, inflammation is closely linked to OS and may establish a vicious loop that is capable of disruption to male reproductive tissues. The result is exaggeration of cellular damage and disruption of male reproductive tissues. Therefore, limitations of antioxidant therapy in treating male infertility are the failure in the selection of specific treatments targeting inflammation and OS simultaneously, two of the core mechanisms of male infertility. The present review aims to elucidate the antioxidant paradox in male infertility treatment, from the viewpoints of both induction of reductive stress as well as overlooking the inflammatory consequences.

scholarly journals Molecular Mechanisms Underlying the Relationship between Obesity and Male Infertility

Metabolites ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 840
Author(s):  
Federica Barbagallo ◽  
Rosita A. Condorelli ◽  
Laura M. Mongioì ◽  
Rossella Cannarella ◽  
Laura Cimino ◽  
...  
Keyword(s):  
Male Infertility ◽  
Molecular Mechanisms ◽  
Premature Mortality ◽  
Male Reproduction ◽  
Increased Risk ◽  
Inflammatory Processes ◽  
Prevalence Of Obesity ◽  
Treatment Of Obesity ◽  
The Relationship ◽  
And Oxidative Stress

In recent decades, the worldwide prevalence of obesity has risen dramatically and is currently estimated to be around 20%. Obesity is linked to an increased risk of comorbidities and premature mortality. Several studies have shown that obesity negatively impacts male fertility through various mechanisms. This review aims to investigate the molecular mechanisms through which obesity impairs male reproduction, including obesity-associated hypogonadism and its effects on spermatogenesis, chronic inflammation, and oxidative stress. Obesity negatively impacts both conventional and biofunctional sperm parameters, and it also induces epigenetic changes that can be transferred to offspring. Moreover, obesity-related diseases are linked to a dysregulation of adipocyte function and micro-environmental inflammatory processes. The dysregulated adipokines significantly influence insulin signaling, and they may also have a detrimental effect on testicular function. Sirtuins can also play an important role in inflammatory and metabolic responses in obese patients. Understanding the molecular mechanisms that are involved in obesity-induced male infertility could increase our ability to identify novel targets for the prevention and treatment of obesity and its related consequences.

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.

Involvement of Heme Oxygenase-1 in Neuropsychiatric and Neurodegenerative Diseases

2018 ◽  
Vol 24 (20) ◽  
pp. 2283-2302 ◽  
Author(s):  
Vivian B. Neis ◽  
Priscila B. Rosa ◽  
Morgana Moretti ◽  
Ana Lucia S. Rodrigues
Keyword(s):  
Neurodegenerative Diseases ◽  
Heme Oxygenase ◽  
Therapeutic Potential ◽  
Redox Homeostasis ◽  
Antioxidant Defenses ◽  
Heme Oxygenase 1 ◽  
Physiological Conditions ◽  
And Oxidative Stress ◽  
Defensive Mechanism

Heme oxygenase (HO) family catalyzes the conversion of heme into free iron, carbon monoxide and biliverdin. It possesses two well-characterized isoforms: HO-1 and HO-2. Under brain physiological conditions, the expression of HO-2 is constitutive, abundant and ubiquitous, whereas HO-1 mRNA and protein are restricted to small populations of neurons and neuroglia. HO-1 is an inducible enzyme that has been shown to participate as an essential defensive mechanism for neurons exposed to oxidant challenges, being related to antioxidant defenses in certain neuropathological conditions. Considering that neurodegenerative diseases (Alzheimer’s Disease (AD), Parkinson’s Disease (PD) and Multiple Sclerosis (MS)) and neuropsychiatric disorders (depression, anxiety, Bipolar Disorder (BD) and schizophrenia) are associated with increased inflammatory markers, impaired redox homeostasis and oxidative stress, conditions that may be associated with alterations in HO-levels/activity, the purpose of this review is to present evidence on the possible role of HO-1 in these Central Nervous System (CNS) diseases. In addition, the possible therapeutic potential of targeting brain HO-1 is explored in this review.

The mechanisms involved in obesity-induced male infertility

2020 ◽  
Vol 16 ◽  
Author(s):  
Hamed Heydari ◽  
Rafighe Ghiasi ◽  
Saber Ghaderpour ◽  
Rana Keyhanmanesh
Keyword(s):  
Oxidative Stress ◽  
Metabolic Disease ◽  
Male Infertility ◽  
Male Fertility ◽  
Reproductive Function ◽  
Disease Development ◽  
Significant Evidence ◽  
Male Reproductive Function ◽  
Negative Effect ◽  
And Oxidative Stress

Introduction: Obesity resulted by imbalance between the intake of energy and energy consumption can lead to growth and metabolic disease development in people. Both in obese men and animal models, several studies indicate that obesity leads to male infertility. Objective: This review has discussed some mechanisms involved in obesity-induced male infertility. Method: Online documents were searched through Science Direct, Pubmed, Scopus, and Google Scholar websites dating from 1959 to recognize studies on obesity, kisspeptin, leptin, and infertility. Results: Obesity induced elevated inflammatory cytokines and oxidative stress can affect male reproductive functions including spermatogenesis disorders, reduced male fertility power and hormones involved in hypothalamus-pituitarygonadal axis. Conclusion: There is significant evidence that obesity resulted in male infertility. obesity has negative effect on male reproductive function via several mechanisms such as inflammation and oxidative stress.

scholarly journals Endogenous formaldehyde scavenges cellular glutathione resulting in cytotoxic redox disruption

2020 ◽  
Author(s):  
Carla Umansky ◽  
Agustín Morellato ◽  
Marco Scheidegger ◽  
Matthias Rieckher ◽  
Manuela R. Martinefski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Fanconi Anemia ◽  
Redox Homeostasis ◽  
Thiol Group ◽  
Cellular Damage ◽  
Repair Pathway ◽  
Cellular Redox ◽  
Redox Active ◽  
Development And Aging

AbstractFormaldehyde (FA) is a ubiquitous endogenous and environmental metabolite that is thought to exert cytotoxicity through DNA and DNA-protein crosslinking. We show here that FA can cause cellular damage beyond genotoxicity by triggering oxidative stress, which is prevented by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR). Mechanistically, we determine that endogenous FA reacts with the redox-active thiol group of glutathione (GSH) forming S-hydroxymethyl-GSH, which is metabolized by ADH5 yielding reduced GSH thus preventing redox disruption. We identify the ADH5-ortholog gene in Caenorhabditis elegans and show that oxidative stress also underlies FA toxicity in nematodes. Moreover, we show that endogenous GSH can protect cells lacking the Fanconi Anemia DNA repair pathway from FA, which might have broad implications for Fanconi Anemia patients and for healthy BRCA2-mutation carriers. We thus establish a highly conserved mechanism through which endogenous FA disrupts the GSH-regulated cellular redox homeostasis that is critical during development and aging.

scholarly journals Melatonin Effect on Cryopreserved Sperm Cells of Crioulo Stallions

2020 ◽  
Vol 5 (2) ◽  
pp. 1-8
Author(s):  
Eraldo L Zanella
Keyword(s):  
Plasma Membrane ◽  
Sperm Motility ◽  
Membrane Integrity ◽  
Male Gamete ◽  
The Body ◽  
Cellular Damage ◽  
Ros Generation ◽  
Sperm Cells ◽  
Beneficial Effects ◽  
Endogenous Antioxidant

The freezing/thawing process of spermatozoa can cause cellular damage to the male gamete, decreasing the fertilization potential due to the increase in the production of reactive oxygen species (ROS). Melatonin is a potent endogenous antioxidant that protects the body against the damage caused by ROS. This study has evaluated different melatonin concentrations on the sperm viability of cryopreserved semen of Crioulo stallions. For that, three ejaculates were collected from five stallions diluted in a commercial extender followed by centrifugation and resuspension in a commercial freezing extender supplemented with 0; 1.25; 2.5. 5mM of Melatonin before the cryopreservation process. After thawing, the evaluation was performed assessing motility and flow cytometry evaluations: the plasma membrane integrity (PI), the integrity of the acrosomal membrane (FITC-PNA), mitochondrial membrane potential (JC1), and ROS generation (DCF-DA). Our results showed that sperm motility in the group without Melatonin and the 1.25mM group did not show the difference; however, the groups 2.5mM and 5mM presented a reduction in sperm motility. The 1.25 mM concentration was able to protect the plasma membrane during the cryopreservation process, in addition to showing a significant reduction in the production of ROS and increasing the percentage of sperm with integral acrosome. It can also be seen that high concentrations of Melatonin did not show beneficial effects. In conclusion, the addition of 1.25 mM of the Melatonin in Crioulo sperm cells showed to have a protective effect on the sperm cell during cryopreservation.

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 The Ameliorating Effect of Berberine-Rich Fraction against Gossypol-Induced Testicular Inflammation and Oxidative Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Samar R. Saleh ◽  
Rana Attia ◽  
Doaa A. Ghareeb
Keyword(s):  
Oxidative Stress ◽  
Male Infertility ◽  
Corn Oil ◽  
Semen Quality ◽  
Experimental Period ◽  
Male Rats ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Interleukin 12 ◽  
Sprague Dawley ◽  
And Oxidative Stress

This study was aimed at evaluating the efficacy of berberine-rich fraction (BF) as a protective and/or a therapeutic agent against inflammation and oxidative stress during male infertility. Sexually mature Sprague-Dawley male rats were divided into five groups treated with either corn oil, BF (100 mg/kg BW, orally, daily for 30 days), gossypol acetate (5 mg/kg BW, i.p.) eight times for 16 days, BF alone for 14 days then coadministered with gossypol acetate for the next 16 days (protected group), or gossypol acetate for 16 days then treated with BF for 30 days (treated group). All animals completed the experimental period (46 days) without obtaining any treatments in the gap period. Sperm parameters, oxidative index, and inflammatory markers were measured. Gossypol injection significantly decreased the semen quality and testosterone level that resulted from the elevation of testicular reactive oxygen and nitrogen species (TBARS and NO), TNF-α, TNF-α-converting enzyme, and interleukins (IL-1β, IL-6, and IL-18) by 230, 180, 12.5, 97.9, and 300%, respectively, while interleukin-12 and tissue inhibitors of metalloproteinases-3 were significantly decreased by 59 and 66%, respectively. BF (protected and treated groups) significantly improved the semen quality, oxidative stress, and inflammation associated with male infertility. It is suitable to use more advanced studies to validate these findings.

Abstract P492: Putative Protein Biomarkers For Reductive Stress Cardiomyopathy

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Rajasekaran Namakkal-Soorappan ◽  
Cynthia L David ◽  
Krishna Parsawar
Keyword(s):  
Protein Quality ◽  
Redox Homeostasis ◽  
Differentially Expressed ◽  
Related Factor ◽  
Protein Biomarkers ◽  
Heat Map ◽  
Reductive Stress ◽  
Tandem Mass Tag ◽  
Map Analysis ◽  
Dose Dependent

Background: Nuclear factor erythroid 2-related factor 2 (NRF2) signaling is vital for redox homeostasis. We reported that transgenic mice expressing constitutively active Nrf2 (CaNrf2) exhibit reductive stress (RS). Here in, we identified novel protein signatures reacting to RS-induced cardiomyopathy. Methods: Tandem Mass Tag (TMT) proteomic analysis was performed in the heart tissues of Ca-Nrf2-transgenic (TG-low & TG-high) and non-transgenic (NTg) mice at 6 months of age (N= 4/group). Differentially expressed proteins (DEPs) were then identified using Scaffold. Validated the key DEPs using immunoblotting. PANTHER and STRING analysis were used to identify potential targets and their interactions. Results: A total of 1105 proteins were extracted from 24369 spectra. Of note, 226 and 261 proteins were differentially expressed in TG-L and TG-H vs. NTg hearts indicating a unique proteome signature for RS. Heat map analysis revealed a clear distinction between the TG-L and TG-H due to the dose-dependent effects of transgene/RS. Majority of the DEPs that are significantly altered in RS mice found to involve in stress related pathways such as antioxidants, NADPH, protein quality control (PQC), etc. Interestingly, some of these proteins were redox modified at their cysteine residues under chronic RS setting. Conclusions: TMT based proteomic analyses revealed unique proteome signatures for RS. The cysteine modifications in multiple proteins likely to cause pathological alterations via impaired PQC mechanisms. Molecular studies related to RS-mediated redox modifications in structural and functional cardiac proteome are underway.

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