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 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.

Carboxylesterase overexpression in the male reproductive tract: a universal safeguarding mechanism?

1999 ◽  
Vol 11 (3) ◽  
pp. 133 ◽  
Author(s):  
A. T. Mikhailov ◽  
M. Torrado
Keyword(s):  
Reproductive Tract ◽  
Expression Patterns ◽  
Cell Lineage ◽  
Environmental Chemicals ◽  
Male Reproductive Tract ◽  
Morphological Organization ◽  
Associated Functions ◽  
And Function ◽  
Hypothetical Explanation

Data on expression patterns of carboxylesterases in the male reproductive tract of different animal groups (i.e. bivalve mollusks, fruitflies and rodents) are summarized to highlight some particularly interesting questions in the context of sperm differentiation, maturation and function. The male reproduc-tive system, in spite of extreme variation in the anatomical/morphological organization in different species, is characterized by similar patterns of male-dependent carboxylesterase overexpression. The phenomenon of conserved carboxylesterase overexpression indicates similar male sex-associated functions of the enzymes. There is possible evidence of carboxylesterase recruitment by male reproductive-tract tissues indi-cating that it could be adaptive for spermatogenesis, sperm maturation and sperm use. Moreover, this idea can be extended to include a sperm cell lineage protection. This issue is discussed in the light of recent data on environmental reproductive xenobiotics that can provide a basis for a hypothetical explanation of car-boxylesterase overexpression in the male reproductive tract. Based on a well-known role of car-boxylesterases in detoxification of environmental chemicals such as organophosphate pesticides, it is proposed that various male genital tract carboxylesterases may be characterized by a similar physiological function to protect the male reproductive system against xenobiotic influences that could provoke its dys-function, thus altering sperm differentiation and maturation.

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 ATP secretion in the male reproductive tract: essential role of CFTR

2012 ◽  
Vol 590 (17) ◽  
pp. 4209-4222 ◽  
Author(s):  
Ye Chun Ruan ◽  
Winnie W. C. Shum ◽  
Clémence Belleannée ◽  
Nicolas Da Silva ◽  
Sylvie Breton
Keyword(s):  
Essential Role ◽  
Reproductive Tract ◽  
Male Reproductive Tract ◽  
Atp Secretion

scholarly journals Estrogen Modulates Glycerol Permeability in Sertoli Cells through Downregulation of Aquaporin-9

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 153 ◽  
Author(s):  
Raquel Bernardino ◽  
David Carrageta ◽  
Ana Silva ◽  
Giuseppe Calamita ◽  
Marco Alves ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Reproductive Tract ◽  
Fluid Secretion ◽  
Male Reproductive Tract ◽  
Aquaporin 9 ◽  
Important Regulator ◽  
17Β Estradiol ◽  
And Function ◽  
Glycerol Permeability

High 17β-Estradiol (E2) levels are known to cause alterations of spermatogenesis and environments throughout the male reproductive tract. Sertoli cells (SCs) ensure an adequate environment inside the seminiferous tubule. Glycerol stands as essential for the maintenance of blood–testis barrier created by SCs, however, the role of E2 in this process is not known. Herein, we hypothesized that the effect of E2 on glycerol permeability in mouse SCs (mSCs) could be mediated by aquaglyceroporins. The expression of aquaglyceroporins was assessed by RT-PCR and qRT-PCR. Glycerol permeability was evaluated by stopped-flow light scattering. We were able to identify the expression of AQP3 and AQP9 in mSCs where AQP9 is more abundant than AQP3. Our results show that high E2 levels decrease AQP9 mRNA abundance with no influence on AQP3 in mSCs. Interestingly, high E2 levels decreased mSCs’ permeability to glycerol, while downregulating AQP9 expression, thus suggesting a novel mechanism by which E2 modulates fluid secretion in the testis. In conclusion, E2 is an important regulator of mSCs physiology and secretion through changes in AQP9 expression and function. Thus, alterations in glycerol permeability induced by E2 may be the cause for male infertility in cases associated with the presence of high E2 levels.

Changes in distribution of labile zinc in mouse spermatozoa during maturation in the epididymis assessed by the fluorophore Zinquin

1996 ◽  
Vol 8 (7) ◽  
pp. 1097 ◽  
Author(s):  
PD Zalewski ◽  
X Jian ◽  
LL Soon ◽  
WG Breed ◽  
RF Seamark ◽  
...  
Keyword(s):  
Sodium Dodecyl Sulfate ◽  
Reproductive Tract ◽  
Regional Distribution ◽  
Sodium Dodecyl ◽  
Sperm Head ◽  
Male Reproductive Tract ◽  
Intracellular Location ◽  
And Function ◽  
Triton X

The Zn(II)-specific fluorophore Zinquin was used to determine the regional distribution of free or loosely-bound Zn(II) in mouse spermatozoa. Spermatozoa from the testes exhibited bright fluorescence over the entire head; those from the caput epididymides generally fluoresced more brightly in the post-acrosomal region; and spermatozoa from the caudae epididymides fluoresced less brightly, with foci of fluorescence over the sperm head which were lost after extraction with Triton X-100 and hence appeared to be membrane-associated. Treatment of cauda sperm with sodium dodecyl sulfate resulted in a bright uniform Zinquin fluorescence in the heads, similar to that observed in caput sperm, indicating that the two types of sperm have similar amounts of head Zn(II) but that the availability of Zn(II) for binding Zinquin is different. By contrast, the intensity of tail fluorescence was similar in spermatozoa from different regions of the male reproductive tract and was largely unaffected by Triton X-100 extraction, consistent with an intracellular location. Similar differences were observed between caput sperm and cauda sperm in the rat. It is concluded that visualization and measurement of free or loosely-bound Zn(II) in subcellular compartments of spermatozoa should facilitate investigation of the role of this metal in the development and function of spermatozoa and abnormalities that might accompany infertility and Zn(II) deficiency.

Role of exosomes in sperm maturation during the transit along the male reproductive tract

2005 ◽  
Vol 35 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Robert Sullivan ◽  
Fabrice Saez ◽  
Julie Girouard ◽  
Gilles Frenette
Keyword(s):  
Reproductive Tract ◽  
Sperm Maturation ◽  
Male Reproductive Tract

scholarly journals The Transformative Impact of Extracellular Vesicles on Developing Sperm

2021 ◽  
Author(s):  
Michael P Rimmer ◽  
Christopher D Gregory ◽  
Rod T Mitchell
Keyword(s):  
Extracellular Vesicles ◽  
Acrosome Reaction ◽  
Reproductive Tract ◽  
Seminiferous Tubules ◽  
Parent Cell ◽  
Male Reproductive Tract ◽  
Future Fertility ◽  
Cell Niche ◽  
Transformative Impact

Objective To review the role of extracellular vesicles (EVs) released from the male reproductive tract and their impact on developing sperm. We discuss how sperm exiting the seminiferous tubules, although developmentally mature, require further modification. Acquisition of various functions including increased motility, transfer of cargoes and ability to undertake the acrosome reaction are mediated through the interaction between sperm and EVs. Methods A review of the literature identified that EVs are released from different portions of the male reproductive tract, notably the epididymis and prostate. These EVs interact with sperm as they pass from the seminiferous tubules to the epididymis and vas deferens prior to ejaculation. Results EVs are small lipid bound particles carrying bespoke RNA, protein and lipid cargoes. These cargoes are loaded based on the state of the parent cell and are used to communicate with recipient cells. In sperm, these cargoes are essential for post testicular modification. Sperm extracted from the proximal epididymis are poorly motile and unable to carry out the acrosome reaction. Conclusions Interaction between developing sperm and EVs is important for the subsequent function of sperm. Little is known however about EVs released from the seminiferous tubules to developing sperm or in the fetal and pre-pubertal testes. A greater understanding, especially in the formation and development of the spermatogonial stem cell niche may lead to new insights as to how damage to this niche may be prevented and preserve future fertility.

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.

Role of Estrogens in the Male Reproductive Tract

2004 ◽  
pp. 89-112
Author(s):  
E. R. Simpson ◽  
S. McPherson ◽  
M. Jones ◽  
K. Robertson ◽  
W. C. Boon ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Male Reproductive Tract
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