scholarly journals Mitochondrial Functionality in Male Fertility: From Spermatogenesis to Fertilization

Antioxidants ◽  
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.

The Effect of PDE5 Inhibitors on the Male Reproductive Tract

2020 ◽  
Vol 26 ◽  
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.

scholarly journals Male Infertility, Oxidative Stress and Antioxidants

2021 ◽  
Author(s):  
Vegim Zhaku ◽  
Ashok Agarwal ◽  
Sheqibe Beadini ◽  
Ralf Henkel ◽  
Renata Finelli ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Male Infertility ◽  
Male Fertility ◽  
Reproductive Tract ◽  
Healthy Lifestyle ◽  
Free Radical Scavengers ◽  
Semen Parameters ◽  
Ros Production ◽  
Modus Operandi ◽  
Male Reproductive Tract

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.

scholarly journals Comparative analysis of activins A and B in the adult mouse epididymis and vas deferens

Reproduction ◽  
2018 ◽  
Vol 155 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Rukmali Wijayarathna ◽  
David M de Kretser ◽  
Rajini Sreenivasan ◽  
Helen Ludlow ◽  
Ralf Middendorff ◽  
...  
Keyword(s):  
Adult Mouse ◽  
Reproductive Tract ◽  
Vas Deferens ◽  
Activin A ◽  
Wild Type ◽  
Male Reproductive Tract ◽  
Epididymal Maturation ◽  
Structural Differences ◽  
Mouse Epididymis

Activin A regulates testicular and epididymal development, but the role of activin B in the epididymis and vas deferens is unknown. Mouse models with reduced activin A (Inhba+/− and InhbaBK/+), or its complete absence (InhbaBK/BK), were investigated to identify specific roles of activins in the male reproductive tract. In 8-week-old Inhba+/− mice, serum activin A decreased by 70%, with a 50% reduction of gene expression and protein in the testis, epididymis and vas deferens. Activin B and the activin-binding protein, follistatin, were similar to wild-type. Testis weights were slightly reduced in Inhba+/− mice, but the epididymis and vas deferens were normal, while the mice were fertile. Activin A was decreased by 70% in the serum, testis, epididymis and vas deferens of InhbaBK/+ mice and was undetectable in InhbaBK/BK mice, but activin B and follistatin levels were similar to wild-type. In 6-week-old InhbaBK/BK mice, testis weights were 60% lower and epididymal weights were 50% lower than in either InhbaBK/+ or wild-type mice. The cauda epididymal epithelium showed infoldings and less intra-luminal sperm, similar to 3.5-week-old wild-type mice, but at 8 weeks, no structural differences in the testis or epididymis were noted between InhbaBK/BK and wild-type mice. Thus, Inhbb can compensate for Inhba in regulating epididymal morphology, although testis and epididymal maturation is delayed in mice lacking Inhba. Crucially, reduction or absence of activin A, at least in the presence of normal activin B levels, does not lead to major defects in the adult epididymis or vas deferens.

scholarly journals Peroxiredoxin 6: The Protector of Male Fertility

Antioxidants ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 173 ◽  
Author(s):  
Cristian O’Flaherty
Keyword(s):  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Antioxidant Protection ◽  
Paternal Genome ◽  
Complex Process ◽  
Epididymal Maturation ◽  
Primary Antioxidant ◽  
Calcium Independent Phospholipase A2

The spermatozoon is a terminal cell with the unique purpose of delivering the paternal genome to the oocyte during fertilization. Once spermatozoa enter into the female reproductive tract, they count on only the antioxidant protection that they received during spermatogenesis and epididymal maturation. Peroxiredoxins (PRDXs), particularly PRDX6, are important players in the antioxidant protection and regulation of reactive oxygen species (ROS) levels in spermatozoa. PRDX6, through its peroxidase and calcium-independent phospholipase A2 activities, plays a major role in the regulation of ROS to maintain viability and motility and allow the spermatozoon to achieve fertilizing ability during the complex process of capacitation. The absence of PRDX6 is sufficient to promote abnormal reproductive outcomes in mice that resemble what we observe in infertile men. Indeed, Prdx6−/− spermatozoa display low motility and severe DNA damage, which is translated into reduced ability to fertilize oocytes in vitro or produce a low number of pups compared to wild-type controls. This review focuses on the role of PRDX6 as the primary antioxidant enzyme that protects the spermatozoon from oxidative-stress-associated damages to protect the paternal genome and assure fertility.

scholarly journals Estrogen-Dependent and -Independent Estrogen Receptor-α Signaling Separately Regulate Male Fertility

Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2898-2905 ◽  
Author(s):  
Kerstin W. Sinkevicius ◽  
Muriel Laine ◽  
Tamara L. Lotan ◽  
Karolina Woloszyn ◽  
John H. Richburg ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Male Fertility ◽  
Reproductive Tract ◽  
Cell Function ◽  
Critical Role ◽  
Estrogen Receptor Α ◽  
Male Reproductive Tract ◽  
Efferent Ductule

Estrogen receptor-α (ERα) plays a critical role in male reproductive tract development and fertility. To determine whether estrogen-dependent and -independent ERα mechanisms are involved in male fertility, we examined male estrogen nonresponsive ERα knock-in mice. These animals have a point mutation (G525L) in the ligand-binding domain of ERα that significantly reduces interaction with, and response to, endogenous estrogens but does not affect growth factor activation of ligand-independent ERα pathways. Surprisingly, we found that ligand-independent ERα signaling is essential for concentrating epididymal sperm via regulation of efferent ductule fluid reabsorption. In contrast, estrogen-dependent ERα signaling is required for germ cell viability, most likely through support of Sertoli cell function. By treating estrogen nonresponsive ERα knock-in (ENERKI) mice with the ERα selective synthetic agonist propyl pyrazole triol, which is able to bind and activate G525L ERα in vivo, we discovered male fertility required neonatal estrogen-mediated ERα signaling. Thus, our work indicates both estrogen-dependent and -independent pathways play separable roles in male murine reproductive tract development and that the role of ERα in human infertility should be examined more closely.

Role of Acid/Base Transporters in the Male Reproductive Tract and Potential Consequences of Their Malfunction

Physiology ◽  
2005 ◽  
Vol 20 (6) ◽  
pp. 417-428 ◽  
Author(s):  
Nuria Pastor-Soler ◽  
Christine Piétrement ◽  
Sylvie Breton
Keyword(s):  
Environmental Factors ◽  
Male Fertility ◽  
Reproductive Tract ◽  
Sperm Maturation ◽  
Genetic Mutations ◽  
Acid Base ◽  
Male Reproductive Tract ◽  
Acidification Capacity ◽  
And Storage

Acid/base transporters play a key role in establishing an acidic luminal environment for sperm maturation and storage in the male reproductive tract. Impairment of the acidification capacity of the epididymis, via either genetic mutations or exposure to environmental factors, may have profound consequences on male fertility.

Role of V-ATPase-rich cells in acidification of the male reproductive tract.

1997 ◽  
Vol 200 (2) ◽  
pp. 257-262 ◽  
Author(s):  
D Brown ◽  
P J Smith ◽  
S Breton
Keyword(s):  
Male Fertility ◽  
Reproductive Tract ◽  
Vas Deferens ◽  
Apical Membrane ◽  
Major Contributor ◽  
Physiological Control ◽  
Male Reproductive Tract ◽  
Secretory Pathways ◽  
Immunocytochemical Detection

Specialized proton-secreting cells play important physiological roles in a variety of tissues. On the basis of the immunocytochemical detection of carbonic anhydrase and V-ATPase in distinct epithelial cells of the epididymis and vas deferens, we predicted that the vacuolar V-ATPase that is located on the apical membrane of these cells should be a major contributor to luminal acidification in parts of the male reproductive tract. Physiological studies using the proton-selective vibrating probe in the vas deferens confirmed this hypothesis. As discussed recently, maintenance of the pH of the reproductive tract is probably under tight physiological control, by analogy with the situation in the kidney. Manipulation of luminal pH might, therefore, provide a point of intervention for the regulation of male fertility. In addition, it is possible that some cases of unexplained male infertility might result from defective acidification, resulting either from pathological states or potentially from environmental factors that may inhibit proton secretory pathways.

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

2019 ◽  
Vol 116 (37) ◽  
pp. 18498-18506 ◽  
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.

scholarly journals Zinc: A Necessary Ion for Mammalian Sperm Fertilization Competency

2018 ◽  
Vol 19 (12) ◽  
pp. 4097 ◽  
Author(s):  
Karl Kerns ◽  
Michal Zigo ◽  
Peter Sutovsky
Keyword(s):  
Male Fertility ◽  
Reproductive Tract ◽  
Zinc Supplementation ◽  
Female Reproductive Tract ◽  
Sperm Maturation ◽  
Cellular Mechanisms ◽  
Human Reproductive ◽  
Semen Processing ◽  
New Research ◽  
And Function

The importance of zinc for male fertility only emerged recently, being propelled in part by consumer interest in nutritional supplements containing ionic trace minerals. Here, we review the properties, biological roles and cellular mechanisms that are relevant to zinc function in the male reproductive system, survey available peer-reviewed data on nutritional zinc supplementation for fertility improvement in livestock animals and infertility therapy in men, and discuss the recently discovered signaling pathways involving zinc in sperm maturation and fertilization. Emphasis is on the zinc-interacting sperm proteome and its involvement in the regulation of sperm structure and function, from spermatogenesis and epididymal sperm maturation to sperm interactions with the female reproductive tract, capacitation, fertilization, and embryo development. Merits of dietary zinc supplementation and zinc inclusion into semen processing media are considered with livestock artificial insemination (AI) and human assisted reproductive therapy (ART) in mind. Collectively, the currently available data underline the importance of zinc ions for male fertility, which could be harnessed to improve human reproductive health and reproductive efficiency in agriculturally important livestock species. Further research will advance the field of sperm and fertilization biology, provide new research tools, and ultimately optimize semen processing procedures for human infertility therapy and livestock AI.

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