Male Infertility, Oxidative Stress and Antioxidants

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 of the experts about the clinical efficacy of antioxidant therapy is still deprived. Prominently, antioxidant such as coenzyme Q10, vitamin C and E, lycopene, carnitine, zinc and selenium have been found useful in controlling the balance between ROS production and scavenging activities. In spite of that, healthy lifestyle, without smoke and alcohol, everyday exercise, reduction of psychological stress and quality well-designed meals, are habits that can overturn male infertility.

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Oxidative Stress, Testicular Inflammatory Pathways and Male Reproduction

International Journal of Molecular Sciences ◽

10.3390/ijms221810043 ◽

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.

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Molecular Changes Induced by Oxidative Stress that Impair Human Sperm Motility

Antioxidants ◽

10.3390/antiox9020134 ◽

2020 ◽

Vol 9 (2) ◽

pp. 134 ◽

Cited By ~ 10

Author(s):

Karolina Nowicka-Bauer ◽

Brett Nixon

Keyword(s):

Oxidative Stress ◽

Sperm Motility ◽

Reproductive Tract ◽

Therapeutic Interventions ◽

Antioxidant Defenses ◽

Ros Production ◽

Paternal Genome ◽

Male Reproductive Tract ◽

Ability To Act ◽

The Impact

A state of oxidative stress (OS) and the presence of reactive oxygen species (ROS) in the male reproductive tract are strongly correlated with infertility. While physiological levels of ROS are necessary for normal sperm functioning, elevated ROS production can overwhelm the cell’s limited antioxidant defenses leading to dysfunction and loss of fertilizing potential. Among the deleterious pleiotropic impacts arising from OS, sperm motility appears to be particularly vulnerable. Here, we present a mechanistic account for how OS contributes to altered sperm motility profiles. In our model, it is suggested that the abundant polyunsaturated fatty acids (PUFAs) residing in the sperm membrane serve to sensitize the male germ cell to ROS attack by virtue of their ability to act as substrates for lipid peroxidation (LPO) cascades. Upon initiation, LPO leads to dramatic remodeling of the composition and biophysical properties of sperm membranes and, in the case of the mitochondria, this manifests in a dissipation of membrane potential, electron leakage, increased ROS production and reduced capacity for energy production. This situation is exacerbated by the production of cytotoxic LPO byproducts such as 4-hydroxynonenal, which dysregulate molecules associated with sperm bioenergetic pathways as well as the structural and signaling components of the motility apparatus. The impact of ROS also extends to lesions in the paternal genome, as is commonly seen in the defective spermatozoa of asthenozoospermic males. Concluding, the presence of OS in the male reproductive tract is strongly and positively correlated with reduced sperm motility and fertilizing potential, thus providing a rational target for the development of new therapeutic interventions.

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Mitochondrial Functionality in Male Fertility: From Spermatogenesis to Fertilization

Antioxidants ◽

10.3390/antiox10010098 ◽

2021 ◽

Vol 10 (1) ◽

pp. 98

Author(s):

Yoo-Jin Park ◽

Myung-Geol Pang

Keyword(s):

Male Infertility ◽

Male Fertility ◽

Reproductive Tract ◽

Female Reproductive Tract ◽

Ros Generation ◽

Male Reproductive Tract ◽

Proteomic Data ◽

Epididymal Maturation ◽

Sperm Dna

Mitochondria are structurally and functionally distinct organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS), to provide energy to spermatozoa. They can also produce reactive oxidation species (ROS). While a moderate concentration of ROS is critical for tyrosine phosphorylation in cholesterol efflux, sperm–egg interaction, and fertilization, excessive ROS generation is associated with male infertility. Moreover, mitochondria participate in diverse processes ranging from spermatogenesis to fertilization to regulate male fertility. This review aimed to summarize the roles of mitochondria in male fertility depending on the sperm developmental stage (from male reproductive tract to female reproductive tract). Moreover, mitochondria are also involved in testosterone production, regulation of proton secretion into the lumen to maintain an acidic condition in the epididymis, and sperm DNA condensation during epididymal maturation. We also established the new signaling pathway using previous proteomic data associated with male fertility, to understand the overall role of mitochondria in male fertility. The pathway revealed that male infertility is associated with a loss of mitochondrial proteins in spermatozoa, which induces low sperm motility, reduces OXPHOS activity, and results in male infertility.

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Male Accessory Glands Infections: Mechanisms of Influence on Male Fertility

Herald Urology ◽

10.21886/2308-6424-2019-7-4-43-48 ◽

2020 ◽

Vol 7 (4) ◽

pp. 43-48 ◽

Cited By ~ 1

Author(s):

I. V. Vinogradov ◽

A. R. Zhivulko ◽

S. V. Korolev

Keyword(s):

Oxidative Stress ◽

Free Radical ◽

Male Infertility ◽

Male Fertility ◽

Chronic Prostatitis ◽

Scientific Data ◽

Semen Parameters ◽

Free Radical Damage ◽

Male Accessory Glands ◽

Accessory Glands

Male accessory glands infections (MAGI) are considered one of the causes of male infertility. Chronic prostatitis is the most prevalent form of MAGI. Researches that assessed the influence of chronic prostatitis on conventional semen parameters have shown contradictory results, so the debate regarding this issue continues. Conventional semen parameters are imperfect markers of male fertility, as many men remain infertile despite being normozoospermic. The search for reliable predictors of male fertility continues to this day. Oxidative stress is considered one of the main pathogenetic mechanisms of male infertility. Free radical oxidation is the leading cause of spermatozoa DNA damage. Spermatozoa DNA fragmentation caused by oxidative stress was associated with a number of unsuccessful reproductive outcomes. There are several factors that are responsible for making spermatozoa vulnerable to free radical damage including abnormal maturation characterized by insufficient chromatin protamination. Acrosin activity defines the ability of spermatozoa to penetrate the ovum membrane and is therefore an independent marker of spermatozoa fertilizing capacity. Possible mechanisms of chronic prostatitis influence on male fertility and current scientific data regarding its association with novel predictors of male infertility are discussed in this article.The study did not have sponsorship. The authors have declared no conflicts of interest.

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The Effect of PDE5 Inhibitors on the Male Reproductive Tract

Current Pharmaceutical Design ◽

10.2174/1381612826666200226121510 ◽

2020 ◽

Vol 26 ◽

Cited By ~ 2

Author(s):

Nikolaos Sofikitis ◽

Aris Kaltsas ◽

Fotios Dimitriadis ◽

Jens Rassweiler ◽

Nikolaos Grivas ◽

...

Keyword(s):

Male Infertility ◽

Reproductive Tract ◽

Tunica Albuginea ◽

Scientific Data ◽

Secretory Function ◽

Pde5 Inhibitors ◽

Male Reproductive Tract ◽

Review Study ◽

Phosphodiesterase 5

The therapeutic range of cyclic nucleotide phosphodiesterase 5 inhibitors (PDE5) inhibitors is getting wider in the last years. This review study focuses on the potential employment of PDE5 inhibitors as an adjunct tool for the therapeutic management of male infertility. The literature tends to suggest a beneficial effect of PDE5 inhibitors on Leydig and Sertoli cells secretory function. It also appears that PDE5 inhibitors play a role in the regulation of the contractility of the testicular tunica albuginea and the epididymis. Moreover scientific data suggest that PDE5 inhibitors enhance the prostatic secretory function leading to an improvement in sperm motility. Other studies additionally demonstrate a role of PDE5 inhibitors in the regulation of sperm capacitation process. Placebo-controlled, randomized, blind studies are necessary to unambiguously incorporate PDE5 inhibitors as an adjunct tool for the pharmaceutical treatment of semen disorders and male infertility.

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The mechanisms involved in obesity-induced male infertility

Current Diabetes Reviews ◽

10.2174/1573399816666200819114032 ◽

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.

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Identification of multiple male reproductive tract-specific proteins that regulate sperm migration through the oviduct in mice

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1908736116 ◽

2019 ◽

Vol 116 (37) ◽

pp. 18498-18506 ◽

Cited By ~ 13

Author(s):

Yoshitaka Fujihara ◽

Taichi Noda ◽

Kiyonori Kobayashi ◽

Asami Oji ◽

Sumire Kobayashi ◽

...

Keyword(s):

Membrane Protein ◽

Male Fertility ◽

Reproductive Tract ◽

Gene Families ◽

Gene Clusters ◽

Mutant Mice ◽

Male Reproductive Tract ◽

Sperm Migration ◽

Specific Proteins ◽

Multiple Male

CRISPR/Cas9-mediated genome editing technology enables researchers to efficiently generate and analyze genetically modified animals. We have taken advantage of this game-changing technology to uncover essential factors for fertility. In this study, we generated knockouts (KOs) of multiple male reproductive organ-specific genes and performed phenotypic screening of these null mutant mice to attempt to identify proteins essential for male fertility. We focused on making large deletions (dels) within 2 gene clusters encoding cystatin (CST) and prostate and testis expressed (PATE) proteins and individual gene mutations in 2 other gene families encoding glycerophosphodiester phosphodiesterase domain (GDPD) containing and lymphocyte antigen 6 (Ly6)/Plaur domain (LYPD) containing proteins. These gene families were chosen because many of the genes demonstrate male reproductive tract-specific expression. AlthoughGdpd1andGdpd4mutant mice were fertile, disruptions ofCstandPategene clusters andLypd4resulted in male sterility or severe fertility defects secondary to impaired sperm migration through the oviduct. While absence of the epididymal protein families CST and PATE affect the localization of the sperm membrane protein A disintegrin and metallopeptidase domain 3 (ADAM3), the sperm acrosomal membrane protein LYPD4 regulates sperm fertilizing ability via an ADAM3-independent pathway. Thus, use of CRISPR/Cas9 technologies has allowed us to quickly rule in and rule out proteins required for male fertility and expand our list of male-specific proteins that function in sperm migration through the oviduct.

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

African Journal of Urology ◽

10.1186/s12301-020-00061-6 ◽

2020 ◽

Vol 26 (1) ◽

Author(s):

Ayad Palani ◽

Ahmed Alahmar

Keyword(s):

Oxidative Stress ◽

Uric Acid ◽

Male Infertility ◽

Seminal Plasma ◽

Case Control Study ◽

Case Control ◽

Semen Parameters ◽

Infertile Men ◽

Total Antioxidant ◽

Control Study

Abstract 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 < 0.0001). However, no significant differences were observed in serum and seminal plasma levels of glutathione, uric acid, albumin and malondialdehyde between infertile and fertile groups. Conclusion Low TAC level induces oxidative stress and consequently causes sperm dysfunction and male infertility. Estimation of TAC can be a useful tool in the diagnosis of male infertility. Antioxidant supplementation should be considered in the treatment of oxidative stress-induced male infertility.

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Mechanisms Associating Improper Diet and Obesity with Infertility

10.32545/encyclopedia202005.0013.v1 ◽

2020 ◽

Author(s):

Kinga Skoracka ◽

Iwona Krela-Kaźmierczak

Keyword(s):

Oxidative Stress ◽

Weight Loss ◽

Male Infertility ◽

High Fat Diet ◽

Male Fertility ◽

Medical Sciences ◽

High Fat ◽

Basic Step ◽

Immunological Disorders ◽

Simultaneous Decrease

Skoracka, K.; Eder, P.; Łykowska-Szuber, L.; Dobrowolska, A.; Krela-Kaźmierczak, I.  Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Heliodor Święcicki Hospital, 60-355 Poznań, Poland A high-fat diet and obesity, the development of which is encouraged by the western lifestyle, can significantly affect male fertility. An inappropriate diet may be directly related to the increase of oxidative stress, but also contribute to the development of obesity, which is associated with the deterioration of fertility, both in terms of generating oxidative stress as well as hormonal or immunological disorders. In obese individuals, disorders on the hypothalamic-pituitary-gonadal axis are observed, as well as elevated oestrogen levels with simultaneous decrease of testosterone, LH and FSH hormone levels. Weight loss in obese men seems to be the first, and the most basic step in the treatment of male infertility.  

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Significance and Relevance of Spermatozoal RNAs to Male Fertility in Livestock

Frontiers in Genetics ◽

10.3389/fgene.2021.768196 ◽

2021 ◽

Vol 12 ◽

Author(s):

Bijayalaxmi Sahoo ◽

Ratan K. Choudhary ◽

Paramajeet Sharma ◽

Shanti Choudhary ◽

Mukesh Kumar Gupta

Keyword(s):

Male Infertility ◽

Male Fertility ◽

Potential Role ◽

Semen Quality ◽

Semen Parameters ◽

Circular Rnas ◽

Reproductive Efficiency ◽

Molecular Signatures ◽

Protein Coding ◽

Non Coding Rnas

Livestock production contributes to a significant part of the economy in developing countries. Although artificial insemination techniques brought substantial improvements in reproductive efficiency, male infertility remains a leading challenge in livestock. Current strategies for the diagnosis of male infertility largely depend on the evaluation of semen parameters and fail to diagnose idiopathic infertility in most cases. Recent evidences show that spermatozoa contains a suit of RNA population whose profile differs between fertile and infertile males. Studies have also demonstrated the crucial roles of spermatozoal RNA (spRNA) in spermatogenesis, fertilization, and early embryonic development. Thus, the spRNA profile may serve as unique molecular signatures of fertile sperm and may play pivotal roles in the diagnosis and treatment of male fertility. This manuscript provides an update on various spRNA populations, including protein-coding and non-coding RNAs, in livestock species and their potential role in semen quality, particularly sperm motility, freezability, and fertility. The contribution of seminal plasma to the spRNA population is also discussed. Furthermore, we discussed the significance of rare non-coding RNAs (ncRNAs) such as long ncRNAs (lncRNAs) and circular RNAs (circRNAs) in spermatogenic events.

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