scholarly journals Immunoregulation in the testis and its implication in fertility and infections

Author(s):  
Kushaan Khambata ◽  
Deepak Modi ◽  
Satish Gupta

The testis is designated as one of the immune previleged sites in the body and harbours a unique immunoregulatory environment, which is important for preventing an immune response against sperm antigens which otherwise are recognized as “foreign” by the immune system. The blood-testis barrier along with the unique immune cells repertoire and various immunoregulatory & immunosuppressive factors secreted by the Leydig cells, Sertoli cells and peritubular cells act in concert to maintain the tolerogenic environment in the testis. Abberations in immunotolerant mechanisms in the testis can lead to generation of anti-sperm antibodies that have an association with male infertility. It can also lead to inflammatory conditions of the male reproductive tract manifested as epididymitis and orchitis, generally due to bacterial or viral infections. In addition, non-infectious epididymitis and orchitis, having autoimmune origin have also been reported in males. While the immune privilege status of human testis protects the germ cells from an immune attack, it can also make the testis a succeptible reservoir for viruses such as human immunodeficiency virus-1, Zika virus and severe acute respiratory syndrome coronavirus-2, all of which have adverse consequences on male reproduction.

2021 ◽  
Author(s):  
Ida Marie Boisen ◽  
John Erik Nielsen ◽  
Lieve Verlinden ◽  
Mette Lorenzen ◽  
Rune Holt ◽  
...  

Vitamin D is important for gonadal function in rodents, and improvement of vitamin D status in men with low sperm counts increases live birth rate. Vitamin D is a regulator of transcellular calcium transport in the intestine and kidney and may influence the dramatic changes in the luminal calcium concentration in epididymis. Here, we show spatial expression in the male reproductive tract of vitamin D receptor (VDR)-regulated factors involved in calcium transport: Transient receptor potential vanilloid 5/6 (TRPV5/6), sodium/calcium exchanger 1 (NCX1), plasma membrane calcium ATPase 1 (PMCA1), calbindin D9k, calcium-sensing receptor (CaSR), and parathyroid hormone-related peptide (PTHrP) in mouse and human testis and epididymis. Testicular Casr expression was lower in Vdr ablated mice compared with controls. Moreover, expression levels of Casr and Pthrp were strongly correlated in both testis and epididymis and Pthrp was suppressed by 1,25(OH)2D3 in a spermatogonial cell line. The expression of CaSR in epididymis may be of greater importance than in the gonad in mice as germ cell-specific Casr deficient mice had no major reproductive phenotype, and coincubation with a CaSR-agonist had no effect on human sperm-oocyte binding. In humans, seminal calcium concentration between 5-10 mM was associated with a higher fraction of motile and morphologically normal sperm cells and the seminal calcium concentration was not associated with serum calcium levels. In conclusion, VDR regulates CaSR and PTHrP, and both factors may be involved in the regulation of calcium transport in the male reproductive tract with possible implications for sperm function and storage.


2021 ◽  
Vol 22 (18) ◽  
pp. 10043
Author(s):  
Sulagna Dutta ◽  
Pallav Sengupta ◽  
Petr Slama ◽  
Shubhadeep Roychoudhury

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.


Author(s):  
Emily A Hixson ◽  
Priya V Borker ◽  
Edwin K Jackson ◽  
Bernard J Macatangay

Abstract Human immunodeficiency virus (HIV) is associated with an increased risk of age-associated comorbidities and mortality compared to people without HIV. This has been attributed to HIV-associated chronic inflammation and immune activation despite viral suppression. The adenosine pathway is an established mechanism by which the body regulates persistent inflammation in order to limit tissue damage associated with inflammatory conditions. However, HIV infection is associated with derangements in the adenosine pathway that limits its ability to control HIV-associated inflammation. This article reviews the function of purinergic signaling and the role of the adenosine signaling pathway in HIV-associated chronic inflammation. This review also discusses the beneficial and potential detrimental effects of pharmacotherapeutic strategies targeting this pathway among people with HIV.


Author(s):  
S. K. Bhure ◽  
P. Harikrishna ◽  
J. Usharani ◽  
A. M. Shende ◽  
S. Harikumar

Regucalcin is a multifunctional protein having an important role in calcium homeostasis, L-ascorbic acid biosynthesis, anti-prolific, anti-apoptotic functions as well as detoxification of chemical warfare nerve agents. Recently, it has been localized to male reproductive tract of rat and human, and identified as an androgen-target gene. The literature suggests a possible role of regucalcin in male fertility. However, no detailed studies have been conducted on its role in male reproductive organs of domestic animals. As an initial step, we had cloned and expressed regucalcin in Pichia pastoris. The sequence analysis showed 100% homology with regucalcin of Bos tours both at nucleotide and amino acid level. The SDS-PAGE and Western blot studies of recombinant protein probed with anti-regucalcin monoclonal antibody showed a higher molecular weight (56 kDa) than the expected (35.5 kDa) that could be due to hyperglycosylation. The recombinant regucalcin and its antibodies can be used to study the detailed role of the protein in male reproduction.


2008 ◽  
Vol 20 (9) ◽  
pp. 105
Author(s):  
T. Reddy ◽  
G. M. Gibbs ◽  
D. J. Merriner ◽  
J. B. Kerr ◽  
M. K. O.'Bryan

Mammalian cysteine rich secretory proteins are a family of four proteins exhibiting a high amino acid sequence similarity and belonging to the CAP (Cysteine rich secretory proteins, Antigen-5 proteins and the plant Pathogenesis related-1 proteins) superfamily of proteins. They are designated CRISP 1, 2, 3 and 4. Structurally, mammalian CRISP’s are characterised by 16 cysteine residues involved in intra-molecular di-sulfide bonds and the formation of 2 domains, ie., the CRISP domain (CD) and CAP domain. Whilst studies on mouse CRISP2 suggest that the CD is involved in ion channel regulation, studies on non-mammalian CAP superfamily members suggest that the CAP domain is involved in proteolytic activity.They are predominantly expressed and localised in the male reproductive tract, however, the EST expression databases suggest that mammalian CRISPs are expressed more widely than in the male reproductive tract. The objective of this study was therefore to conclusively define the expression and localisation of each CRISP protein in a mammalian system.A reverse transcription PCR expression profile and immunohistochemical analysis of 16 mouse tissue was conducted to establish the expression and localisation of each of the four CRISPs. These data showed that although the CRISPs have a strong expression and localisation bias to the male reproductive tract, they are widely distributed throughout the body in mice, including the ovary, uterus, and mammary gland. Whilst each CRISP has a clear expression profile, there was a striking localisation of androgen regulated CRISPs (1, 3, 4) in immune tissue including the spleen and thymus. Such a localisation raises the spectre of a role for CRISPs in the normal physiology and disease of several organs.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Fátima Regina Mena Barreto Silva

The 1α,25(OH)2-vitamin D3 (1,25-D3) is known by its classic effects on Ca2+ metabolism and regulation of cellular proliferation and differentiation. The hormone 1,25-D3 acts in the testis through nongenomic and genomic events being implicated in the success of spermatogenesis in rats and in human being. The aim of this review was to highlight the effect and intracellular pathways of 1,25-D3 to modulate the spermatogenesis. The pivotal role of 1,25-D3 in male reproduction is reinforced by the presence of VDR and 1α-hydroxylase in reproductive tract. Also, the marked expression of VDR and the VD metabolizing enzymes in human testis, ejaculatory tract, and mature spermatozoa implicates the 1,25-D3 in spermatogenesis and maturation of human spermatozoa. Among genomic events, 1,25-D3 influences the expression of calcium binding protein and stimulates aromatase gene expression through a nongenomic activation of the membrane-bound VDR receptor involving the PKA pathway in the testis. Also, 1,25-D3 stimulates amino acid transport and exocytosis in testis by nongenomic events coupled to ionic currents triggered at plasma membrane. All together, the demonstration that 1,25-D3 regulates both Sertoli cell and sperm function may be useful for the study and development of new therapeutic strategies for the male reproductive disorders.


1986 ◽  
Vol 5 (4) ◽  
pp. 209-223 ◽  
Author(s):  
D. P. Waller ◽  
A. R. Nikurs

The purpose of this presentation is to review for toxicologists the structure and functioning of the male reproductive system. Presented are the anatomy, physiology, and biochemistry of the system, along with considerations in evaluating toxic insult to the body.


2021 ◽  
pp. 026010602110496
Author(s):  
Atiyeh Nayebi ◽  
Jamshid Gholizadeh Navashenaq ◽  
Davood Soleimani ◽  
Seyyed Mostafa Nachvak

Background: Despite strategies based on social distancing, the coronavirus disease 2019 (COVID-19) expands globally, and so far, many attempts have been made to achieve effective treatment for patients with COVID-19. This disease infects the lower respiratory tract and may lead to severe acute respiratory syndrome coronavirus (SARS-CoV). COVID-19 also can cause gastrointestinal infections. Therefore, COVID-19 patients with gastrointestinal symptoms are more likely to be complicated by SARS-CoV. In this disease, acquired immune responses are impaired, and uncontrolled inflammatory responses result in cytokine storms, leading to acute lung injury and thrombus formation. Probiotics are living microorganisms that contribute to the health of the host if administered in appropriate doses. Aim: This study aimed to provide evidence to show the importance of gut dysbiosis in viral disease, especially COVID-19. Therefore, we have focused on the impact of probiotics consumption on preventing severe symptoms of the disease. Methods: We have entirely searched SCOPUS, PubMed, and Google Scholar databases to collect evidence regarding the relationship between probiotics and viral infections to expand this relationship to the COVID-19. Results: It has been shown that probiotics directly counteract SARS-CoV in the gastrointestinal and respiratory tracts. Moreover, probiotics suppress severe immune responses and prevent cytokine storms to inhibit pathologic inflammatory conditions in the body via modulation of immune responses. Conclusion: According to available evidence based on their antiviral and respiratory activities, using probiotics might be an adjuvant therapy to reduce the burden and severity of this disease.


2015 ◽  
Author(s):  
Christian L Althaus

In this Opinion piece, I argue that the dynamics of viruses and the cellular immune response depend on the body size of the host. I use allometric scaling theory to interpret observed quantitative differences in the infection dynamics of lymphocytic choriomeningitis virus (LCMV) in mice (Mus musculus), simian immunodeficiency virus (SIV) in rhesus macaques (Macaca mulatta) and human immunodeficiency virus (HIV) in humans. However, additional data on the kinetics of virus replication and the dynamics of T cell responses in different host species will be required to shed more light on the question whether the nature of viral infections is affected by the body size of their hosts.


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