SARS-CoV-2 and the testis: similarity with other viruses and routes of infection.

Since the start of the latest coronavirus (SARS-CoV-2) outbreak, the number of infected individuals and cases of coronavirus disease (COVID-19) has been increasing exponentially worldwide. Of interest is existing evidence that orchitis can develop due coronavirus infection. It is therefore not unreasonable to believe that SARS-CoV-2 could be transmitted by semen. Consequently, it is of paramount importance that individuals who could potentially be infected take all possible care to mitigate the likely risk of passing on the infection through sexual intercourse.

Influence of ejaculation frequency on seminal parameters.

BACKGROUND: Several factors have been shown to influence semen parameters, one of which is sexual abstinence; a clinical criteria included in the semen evaluation to provide maximum sperm quality. The aim of the present study was to assess the effect of a daily ejaculation frequency on conventional and functional semen parameters. METHODS: Semen samples were collected daily over a period of two weeks of which every second sample per person was processed and analyzed according to the World Health Organization guidelines. Furthermore, mitochondrial function, intracellular reactive oxygen species production and sperm DNA fragmentation were evaluated by flow cytometry. RESULTS: Total sperm count and seminal volume per ejaculation declined and remained decreased for the duration of the daily ejaculation period. However, conventional parameters such as sperm concentration, motility, progressive motility, morphology, vitality and functional parameters such as sperm plasma membrane integrity, mitochondrial membrane potential and DNA fragmentation was not significantly affected and remained similar to the initial measurement throughout the daily ejaculation period. Despite intra- and inter individual variations, the average values of the basic semen parameters remained above the WHO (2010) reference values throughout the daily ejaculation period. Interestingly, a decreasing trend in intracellular ROS production was observed, although statistically not significant. CONCLUSIONS: The study shows that an extended 2 week period of daily ejaculation does not have major clinical effects on conventional and functional seminal parameters.

The microbiota of sexual intercourse and its effect on prostatitis.

It is estimated that microorganisms colonize 90% of the body surface. In some tracts, such as the genitourinary tract, the microbiota varies throughout life, influenced by hormonal stimulation and sexual practices. This study evaluated the semen differences and presence of Lactobacillus crispatus, Lactobacillus iners, Gardnerella vaginalis and Atopobium vaginae in semen samples from patients with symptoms of chronic prostatitis and men asymptomatic for urogenital infections. Fifty-three semen samples were included: 22 samples from men with symptoms of chronic prostatitis and 31 asymptomatic men (control group). In addition to the presence of L. crispatus, L. iners, G. vaginalis and A. vaginae, semen parameters, total antioxidant capacity of seminal plasma, prostatic antigen and some proinflammatory cytokines were evaluated in each semen sample. Volunteers with symptoms of chronic prostatitis presented a lower percentage of sperm morphology (4.3% vs. control group 6.0%, p = 0.004); in the semen samples of volunteers in the group asymptomatic for urogenital infections, microorganisms associated with the vaginal microbiota were detected more frequently. The presence of bacteria in the vaginal microbiota can also benefit male reproductive health, which undergoes various modifications related to lifestyle habits that are susceptible to modification. Microorganisms associated with the vaginal microbiota, such as L. crispatus, L. iners, G. vaginalis and A. vaginae, may have a protective role against the development of male genitourinary diseases such as prostatitis.

Effects of nanotubes on semen quality and fertility in humans: A systematic review of literature.

BACKGROUND: In the medical field, it is increasingly common to observe the use of nanotubes, for example, in the administration of drugs. However, nanotubes raise concerns for male fertility due to potential effects on hormone levels and sperm quality observed in animal studies. In addition, animal exposure to multi-walled carbon nanotube models found alterations in hormone levels, sperm motility, and sperm count. Limited evidence in humans suggests no adverse effects, but further research is needed. This study aimed to perform a systematic review to assess the in vitro effects of nanotubes on semen and fertility in humans. METHODS: We included all published in vitro studies about semen or sperm or male fertility and nanotubes in humans. A search was conducted in LILACS, PubMed, and SCOPUS as of May 2023. The risk of bias was assessed using the QUIN tool. RESULTS: Four studies using nanotubes on human sperm were included, nanotubes exposure appears not to affect sperm viability; however, some alterations to motility, velocity and production of reactive oxygen species were reported. Limited evidence is provided because of the small quantity of publications. CONCLUSIONS: Nanotubes appear to have no adverse effects on human sperm.

Leiomyoma of the urinary bladder: a case report.

The case of a 71-year-old woman who presented with one year history of pelvic pain and occasional dysuria is reported. Computed tomography and Magnetic Resonance Imaging revealed a well defined intramural bladder mass. The histological findings of the surgical specimen confirmed a leiomyoma of the urinary bladder. The clinical presentation,imaging findings and management of this relatively rare benign tumor are discussed.

Could exposure to spaceflight cause mutations in genes that affect male fertility?

Recently, a study reported that upon analyzing blood samples from 14 astronauts that flew Space Transportation System missions between 1998 and 2001, 34 somatic nonsynonymous single nucleotide variants were detected in 17 CH-driver genes. Of interest is that the cohort consisted of relatively young astronauts, 85% of which were males of reproductive age. Having investigated the genes with nonsynonymous substitutes from the literature, it was found that twelve of these 17 genes appear to play essential roles in male reproduction. Changes in telomere length and gene regulation were also reported in another study conducted on an astronaut during a long duration stay on the International Space Station. Realizing the impact of spaceflight on gene sequence with potential influence on male fertility, it is important that more studies are conducted in this field. Specifically, in light of ultimately colonizing space, multi-generational survival is crucial and strategies to mitigate or counteract such effects should be explored.

Biological sex and age-related differences shape the antiviral response to SARS-CoV-2 infection.

For the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, clinical manifestations are broad and highly heterogeneous for both sexes. We aimed to determine how biological sex and age impact immune gene expression, particularly influencing the humoral neutralizing antibody (NAb) response and the cytokine production in coronavirus disease 2019 (COVID-19) subjects. The immune gene expression, according to biological sex and age, was assessed using the genome wide expression profile of blood proteins from healthy individuals using the Genotype Tissue Expression (GTEx) database. Moreover, anti-SARS-CoV-2 neutralizing antibody titers and cytokine levels were determined in blood samples from 141 COVID-19 individuals from Medellín, Colombia. Among subjects with COVID-19, males had statistically significantly higher median NAb titers and serum concentrations of interleukin-6 and CC chemokine ligand 3 than females. Overall, our findings point out a more robust innate immune response in women that could help recognize and restrain the virus faster than in men.

Low-level HIV infection of hepatocytes.

BACKGROUND: There are only limited data on whether HIV infection occurs within the liver; therefore, we explored early and late stages of the HIV life cycle in two hepatocyte cell lines--Huh7.5 and Huh7.5JFH1--as well as in primary human hepatocytes. RESULTS: Integrated HIV DNA was detected in Huh7.5 and Huh7.5JFH1 cells, as well as in primary hepatocytes, and was inhibited by the integrase inhibitor raltegravir in a dose-dependent manner. HIV p24 protein was also detected in cell culture supernatants at days 1, 3, 5, and 7 post-infection and was inhibited by AZT, although levels were modest compared to those in a lymphocyte cell line. Culture supernatants from HIV-infected hepatocytes were capable of infecting a non-hepatic HIV indicator cell line. CONCLUSIONS: These results indicating low-level HIV replication in hepatoctyes in vitro complement evidence suggesting that HIV has deleterious effects on the liver in vivo.

Increased exfoliation of immature germ cells detected in semen analysis routine and its clinical significance.

To the Editor, Currently, semen analysis is the unique test to evaluate men's fertility potential. Semen analysis provides valuable information on sperm production and quality. In addition to the conventional assessment of the sperm characteristics in a basic semen analysis routine, performing a differential diagnosis of leukocytes and sperm precursors immature germ cells (IGC) is also pivotal, due to adding valuable and clinically suitable information to the semen report [...].

Molecular analysis of microorganisms in the semen and their impact on semen parameters.

OBJECTIVE: Chronic genitourinary infections can alter male fertility and even promote carcinogenic processes. This study aimed to evaluate the effect of the presence in the semen of microorganisms on semen quality. MATERIALS AND METHODS: Clinical symptoms and conventional and functional seminal parameters of eleven fertile donors and ten volunteers with prostatitis-like symptoms were evaluated. Nitric oxide, antioxidant capacity, and pro-inflammatory cytokines in semen and seminal plasma samples were also quantified. Finally, the expression of the ROR-γT, FoxP3, and T-bet genes in semen and the presence of DNA of microorganisms associated with prostatitis in urine and semen were evaluated. RESULTS: When compared with fertile donors, volunteers with chronic prostatitis-like symptoms reported erectile dysfunction (0% vs. 10%, p = 0.2825) and premature ejaculation (0% vs. 40%; p = 0.0190). No statistically significant differences were observed in seminal parameters, cytokine measurement, antioxidant capacity, nitric oxide concentration and ROR-γT, FoxP3, T-bet. Microorganisms responsible for sexually transmitted infections and some bacteria associated with the microbiota and infections in the prostate gland were detected. In the semen from the subjects with prostatitis-like symptoms T. vaginalis DNA was detected; in addition, N. gonorrhoeae DNA was also detected in semen and urine samples. S. pyogenes was detected in the urine samples from the control group. CONCLUSIONS: Prostatitis-like symptoms are a common finding in young men that affect sexual and reproductive health, but not always the seminal parameters or fertility. The presence of prostatitis- like symptoms does not affect seminal quality. However, it appears to be associated with an increased likelihood of erectile dysfunction and premature ejaculation. Thus, affecting the quality of life and sexual and reproductive health.

Overweight and obesity: The allies of prostate inflammation.

To the Editor, World Health Organization (WHO) defines infertility as the inability of a sexually active partner to achieve a clinically confirmed pregnancy after at least one year of intercourse without contraceptive protection on fertile days. As women are primarily responsible for the conception, childbirth, and postpartum, fertility problems have been related to fertile female capacity. However, men play an essential role, being responsible for about 50% of alterations in fertility due to dysfunctions in the male reproductive tract, including varicocele, hypogonadism, poorly descended testicles, testicular tumors, and even anti-sperm autoantibodies [...].

The relationship between sexually transmitted microorganisms and seminal quality in asymptomatic men.

Objective: To detect DNA of different microorganisms, in semen samples from apparently healthy men and correlate their presence with seminal quality. Methods: Semen samples from 81 healthy volunteers were collected, and semen parameters were analyzed. DNA extraction was performed using the phenol-chloroform technique, and the microorganisms were detected by the amplification of specific primers using polymerase chain reaction. Results: DNA from at least one of the microorganisms was detected in 78 samples. The most frequent microorganism found in semen were: Lactobacillus spp. (70%), Neisseria gonorrhoeae (N. gonorrhoeae) (36%), Streptococcus epidermidis (64%), Klebsiella pneumoniae (56%), Staphylococcus aureus (32%), Chlamydia trachomatis (C. trachomatis) (28%), Pseudomonas aeruginosa (27%). The seminal parameters of all semen samples were over the lower reference values for normal semen analysis. To compare with negative samples, seminal volume was higher for the Escherichia coli positive samples and lower for Pseudomonas aeruginosa positive samples. Semen samples positive for Staphylococcus aureus had worse sperm morphology. The frequency of progressive motility was higher in positive samples for N. gonorrhoeae and C. trachomatis. Positive semen samples for C. trachomatis had a higher concentration per milliliter. Conclusion: It is common to find microorganisms in semen of asymptomatic men, including those responsible for sexually transmitted infections. Antimicrobial treatment is recommended only in those individuals with a sexually transmitted infection (C. trachomatis and N. gonorrhoeae) and always promote condom use.

Mechanisms of SARS-CoV-2 and Male Infertility: Could Connexin and Pannexin Play a Role?

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male infertility has lately received significant attention. SARS-CoV-2, the virus that causes coronavirus disease (COVID-19) in humans, has been shown to impose adverse effects on both the structural components and function of the testis, which potentially impact spermatogenesis. These adverse effects are partially explained by fever, systemic inflammation, oxidative stress, and an increased immune response leading to impaired blood-testis barrier. It has been well established that efficient cellular communication via gap junctions or functional channels is required for tissue homeostasis. Connexins and pannexins are two protein families that mediate autocrine and paracrine signaling between the cells and the extracellular environment. These channel-forming proteins have been shown to play a role in coordinating cellular communication in the testis and epididymis. Despite their role in maintaining a proper male reproductive milieu, their function is disrupted under pathological conditions. The involvement of these channels has been well documented in several physiological and pathological conditions and their designated function in infectious diseases. However, their role in COVID-19 and their meaningful contribution to male infertility remains to be elucidated. Therefore, this review highlights the multivariate pathophysiological mechanisms of SARS-CoV-2 involvement in male reproduction. It also aims to shed light on the role of connexin and pannexin channels in disease progression, emphasizing their unexplored role and regulation of SARS-CoV-2 pathophysiology. Finally, we hypothesize the possible involvement of connexins and pannexins in SARS-CoV-2 inducing male infertility to assist future research ideas targeting therapeutic approaches.

SARS-CoV-2 Vaccine Effects on Semen Parameters: A Systematic Review and Meta-Analysis.

OBJECTIVE: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epitomizes the best preventative SARS-CoV-2 infection strategy to counteract the severe consequences of infection. However, concerns have been raised that the vaccines could have an adverse effect on sperm function and overall reproductive health. This combined systematic review and meta-analysis aimed to investigate the effects of different available SARS-CoV-2 vaccines on semen parameters. METHODS: A systematic PubMed, Scopus, Google Scholar, ScienceDirect, LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud), and Scilit database literature search until mid-June 2022 was conducted. Prospective and retrospective studies were eligible. No limitation was placed on language. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were thereafter obtained. RESULTS: Upon search completion, 122 studies were identified and retrieved and 110 were excluded, while the remaining 12 independent studies evaluating the effects of coronavirus disease 2019 (COVID-19) vaccines on semen parameters were included in this review. The total number of men included was 1551, aged 22.4-48 years. Following meta-analysis, the SMD summary measure with 95% CI for each semen parameter included a concentration of 0.22 (0-0.22); Total sperm count of 0.11 (0.18-0.24); Total motility of 0.02 (0.05-0.09); Volume of 0.02 (-0.1-0.14); Vitality of 0.55 (-0.19-0.29), progressive motility of -0.43 (-0.54 to -0.32); Total motile sperm count of -0.38 (-0.44 to -0.31); And normal morphology of 0.42 (-0.54 to -0.3). In brief, the total sperm count was slightly increased post-vaccination, while progressive motility, total motile sperm count, and normal morphology were marginally reduced post-vaccination, according to the meta-analysis. CONCLUSIONS: No effects were observed regarding sperm viability and semen volume since the results of all the studies crossed the line of no effect. All seminal parameters analyzed showed a negligible or small change in relation to the vaccination effect. Furthermore, the parameters remained within the normal World Health Organization reference ranges, making the clinical significance unclear. Therefore, based on these results, it appears that vaccination does not have negative effects on semen quality. The individual study findings suggested that COVID-19 vaccines are not associated with decreased semen parameters.

Functional Profile of CD8+ T-Cells in Response to HLA-A*02:01-Restricted Mutated Epitopes Derived from the Gag Protein of Circulating HIV-1 Strains from Medellín, Colombia.

CD8+ T-cells play a crucial role in the control of HIV replication. HIV-specific CD8+ T-cell responses rapidly expand since the acute phase of the infection, and it has been observed that HIV controllers harbor CD8+ T-cells with potent anti-HIV capacity. The development of CD8+ T-cell-based vaccine against HIV-1 has focused on searching for immunodominant epitopes. However, the strong immune pressure of CD8+ T-cells causes the selection of viral variants with mutations in immunodominant epitopes. Since HIV-1 mutations are selected under the context of a specific HLA-I, the circulation of viral variants with these mutations is highly predictable based on the most prevalent HLA-I within a population. We previously demonstrated the adaptation of circulating strains of HIV-1 to the HLA-A*02 molecule by identifying mutations under positive selection located in GC9 and SL9 epitopes derived from the Gag protein. Also, we used an in silico prediction approach and evaluated whether the mutations found had a higher or lower affinity to the HLA-A*02. Although this strategy allowed predicting the interaction between mutated peptides and HLA-I, the functional response of CD8+ T-cells that these peptides induce is unknown. In the present work, peripheral blood mononuclear cells from 12 HIV-1+ HLA-A*02:01+ individuals were stimulated with the mutated and wild-type peptides derived from the GC9 and SL9 epitopes. The functional profile of CD8+ T-cells was evaluated using flow cytometry, and the frequency of subpopulations was determined according to their number of functions and the polyfunctionality index. The results suggest that the quality of the response (polyfunctionality) could be associated with the binding affinity of the peptide to the HLA molecule, and the functional profile of specific CD8+ T-cells to mutated epitopes in individuals under cART is maintained.

In Silico Analysis of Sperm From Ejaculates with Different Semen Characteristics.

BACKGROUND: Male infertility is associated with altered characteristics of the sperm within the ejaculate. It is possible to find molecular explanations for the observed phenotypes and their consequences. This study aimed to analyze, using a specialized software, a gene set of transcriptomic data from different types of ejaculates. METHODS: Data from ejaculate samples categorized as normal, oligospermia, and teratozoospermia were obtained from Gene Expression Omnibus (GEO). After normalization, the data average for each sample category was calculated and analyzed independently using Ingenuity Pathway Analysis (IPA). RESULTS: Five important canonical pathways are involved in normal and altered semen samples (Oligospermia and teratozoospermia) except sirtuin signaling and mitochondrial dysfunction pathways. The five most important biological processes are identified in all semen phenotypes, but the only difference is the genes connected with initiation of RNA transcription in oligospermic and asthenospermic samples. CONCLUSION: Surprisingly, different types of ejaculates share many pathways and biological processes; sperm proteomics as a new global approach gives clues for the development of strategies to explain the reason for observed phenotypes of ejaculated spermatozoa, their possible effect on fertility, and for implementing research strategies in the context of infertility diagnosis and treatment.

Microbiota, Prostatitis, and Fertility: Bacterial Diversity as a Possible Health Ally.

BACKGROUND: In health, microorganisms have been associated with the disease, although the current knowledge shows that the microbiota present in various anatomical sites is associated with multiple benefits. OBJECTIVE: This study aimed to evaluate and compare the genitourinary microbiota of chronic prostatitis symptoms patients and fertile men. MATERIALS AND METHODS: In this preliminary study, ten volunteers have included 5 volunteers with symptoms of chronic prostatitis (prostatitis group) and five fertile volunteers, asymptomatic for urogenital infections (control group) matched by age. Bacterial diversity analysis was performed using the 16S molecular marker to compare the microbiota present in urine and semen samples from chronic prostatitis symptoms and fertile volunteers. Seminal quality, nitric oxide levels, and seminal and serum concentration of proinflammatory cytokines were quantified. RESULTS: Fertile men present a greater variety of operational taxonomical units-OTUs in semen (67.5%) and urine (17.6%) samples than chronic prostatitis symptoms men. Chronic prostatitis symptoms men presented a higher concentration of IL-12p70 in seminal plasma. No statistically significant differences were observed in conventional and functional seminal parameters. The species diversity in semen samples was similar in healthy men than prostatitis patients, inverted Simpson index median 5.3 (5.0-10.7) vs. 4.5 (2.1-7.8, p=0.1508). Nevertheless, the microbiota present in the semen and urine samples of fertile men presents more OTUs. Less microbial diversity could be associated with chronic prostatitis symptoms. The presence of bacteria in the genitourinary tract is not always associated with the disease. Understanding the factors that affect the microbiota can implement lifestyle habits that prevent chronic prostatitis. CONCLUSION: Chronic prostatitis does not seem to affect male fertility; however, studies with a larger sample size are required. Our preliminary results strengthen the potential role; the greater bacterial diversity is a protective factor for chronic prostatitis.

SARS-COV-2 (Covid-19) and male fertility: Where are we?

Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), a single-stranded RNA virus, was found to be the causal agent of the disease called coronavirus disease. During December 2019, China informed the World Health Organization (WHO) of an outbreak of cases of pneumonia of unknown etiology, which caused severe-acute respiratory distress. The disease was termed coronavirus disease 2019 (Covid-19). Due to alarming levels of spread and severity, on the 11th of March 2020, the WHO declared the outbreak as a global pandemic. As of September 14, 2020, more than 29 million cases have been reported, with over 900,000 deaths globally. Since the outbreak, although not conclusive, discoveries have been made regarding the understanding of the epidemiology, etiology, clinical features, clinical treatment, and prevention of the disease. SARS-COV-2 has been detected in saliva, respiratory fluids, blood, urine, and faeces. Findings are however controversial regarding its presence in the semen or the testis. Hence, this review aimed to further analyse the literature concerning (i) the effects of previously identified human coronaviruses on male fertility (ii) the impact of Covid-19 on male fertility and (iii) the implication for general health in terms of infection and transmission.