-
Journal of Molecular Histology Oct 2021Multiorgan dysfunction is the main characteristic of severe COVID-19 patients and the involvement of male reproductive system may occur among these patients. Although... (Review)
Review
Multiorgan dysfunction is the main characteristic of severe COVID-19 patients and the involvement of male reproductive system may occur among these patients. Although there is a limited evidence to confirm the orchitis and virus presence in the semen of patients, there are concerns about the transmission of virus through the semen. In addition, reduced fertility or infertility can be seen as consequences of severe COVID-19 in recovered subjects. In this study, we aimed to review articles related to COVID-19 and male reproductive system to find the possible underlying mechanisms of SARS-CoV-2 in affecting male fertility. The following keywords of SARS-CoV-2, COVID-19, testis, orchitis, semen, angiotensin-converting enzyme 2 (ACE2), hypothalamic-pituitary-testicular (HPT) axis, Hypothalamus, etc., were defined to find the related publications from standard search engines, e.g., PUBMED, SCOPUS, Google Scholar. According to studies, COVID-19 occurs in severe patients as respiratory disease, along with multi-organ failure. The most important mechanisms are classified as direct and indirect pathogenesis of SARS-CoV-2. The presence of ACE2 on the cell surface of various cells in testis increases the risk of direct infection by this virus. SARS-CoV-2 also affects the testis through the cytokine storm. In addition, the important role of HPT axis dysregulation through impaired Leydig cells and hypothalamus should be considered. Using antiviral and immunomodulatory therapy can be harmful for testis function. Further investigations are required to investigate potential mechanisms of male infertility in survivals of COVID-19. Since involvement of testis is essential for fertility, increasing the knowledge of health system may improve the outcomes.
Topics: COVID-19; Cytokine Release Syndrome; Genitalia, Male; Humans; Infertility, Male; Male; SARS-CoV-2
PubMed: 34232425
DOI: 10.1007/s10735-021-10003-3 -
Pediatric Surgery International Mar 2015Epididymo-orchitis (EO) is infrequently reported in anorectal malformation (ARM) cases. Therefore, it is difficult to assess its risk factors.
PURPOSE
Epididymo-orchitis (EO) is infrequently reported in anorectal malformation (ARM) cases. Therefore, it is difficult to assess its risk factors.
METHODS
A total of 110 male patients who were operated on for ARM at the same Institution over a period of 13 years were contacted. Association was assessed between EO and the following: spinal dysraphism (SD), symptomatic VUR (VUR), and bowel management (BM) requiring enemas. The data were analyzed with the Chi-square test.
RESULTS
A total of 89 patients were contacted. Ten cases of EO were found, and all occurred in patients with recto-urethral (RU) fistula after reconstruction. The patients' age at first episode ranged between 4 and 11 years. RU fistula patients experiencing EO (Group A, 10 patients) were compared with those without EO (Group B, 33 patients). VUR occurred in 9/10 cases in Group A and in 13/33 cases in group B (Chi-square 7.8658, p = 0.005038). SD was present in 4/10 cases in group A and in 13/33 cases in Group B (Chi-square 0.0434, p = 0.83491). A total of 8/10 cases in Group A and 12/33 cases in Group B were on BM (Chi-square 5.87, p = 0.0015).
CONCLUSIONS
EO occurs in approximately in 20 % of male cases with ARM, and recto-urinary communication and should be considered the primary diagnosis in the presence of testicular pain. This could avoid unnecessary surgical exploration, and the family should be counseled about this subject.
Topics: Abnormalities, Multiple; Anal Canal; Child; Child, Preschool; Epididymitis; Humans; Male; Orchitis; Plastic Surgery Procedures; Rectum; Risk Factors; Treatment Outcome
PubMed: 25652761
DOI: 10.1007/s00383-015-3671-6 -
Cureus Apr 2023Emphysematous epididymo-orchitis is a rare and potentially fatal infection marked by the presence of gas in the epididymis and testicular tissue. Here, we describe the...
Emphysematous epididymo-orchitis is a rare and potentially fatal infection marked by the presence of gas in the epididymis and testicular tissue. Here, we describe the case of a 49-year-old male with a known past medical history of diabetes and hypertension who presented with right inguinoscrotal swelling and severe tenderness. An urgent scrotal ultrasound was obtained and revealed a fluid-filled avascular mass. Moreover, the non-contrast CT scan showed a mixture of air and fluid density in the right epididymis, perineum, and spermatic cord course. The medical team confirmed the diagnosis of emphysematous epididymo-orchitis. The patient refused the management plan at first, but later came back and accepted the procedure. A right orchidectomy with spermatic cord removal was performed without complications.
PubMed: 37266058
DOI: 10.7759/cureus.38358 -
Molecular Human Reproduction Feb 2021Experimental autoimmune orchitis (EAO) is a useful model to study organ-specific autoimmunity and chronic testicular inflammation. This model reflects testicular...
Experimental autoimmune orchitis (EAO) is a useful model to study organ-specific autoimmunity and chronic testicular inflammation. This model reflects testicular pathological changes reported in immunological infertility in men. Progression of EAO in rodents is associated with a significantly increased percentage of testicular endothelial cells and interstitial testicular blood vessels, indicating an ongoing angiogenic process. Vascular endothelial growth factor A (VEGFA), the main regulator of physiological and pathological angiogenesis, can stimulate endothelial cell proliferation, chemotaxis and vascular permeability. The aim of this study was to explore the role of VEGFA in the pathogenesis of testicular inflammation. Our results found VEGFA expression in Leydig cells, endothelial cells and macrophages in testis of rats with autoimmune orchitis. VEGFA level was significantly higher in testicular fluid and serum of rats at the end of the immunization period, preceding testicular damage. VEGF receptor (VEGFR) 1 is expressed mainly in testicular endothelial cells, whereas VEGFR2 was detected in germ cells and vascular smooth muscle cells. Both receptors were expressed in testicular interstitial cells. VEGFR2 increased after the immunization period in the testicular interstitium and VEGFR1 was downregulated in EAO testis. In-vivo-specific VEGFA inhibition by Bevacizumab prevented the increase in blood vessel number and reduced EAO incidence and severity. Our results unveil relevance of VEGFA-VEGFR axis during orchitis development, suggesting that VEGFA might be an early marker of testicular inflammation and Bevacizumab a therapeutic tool for treatment of testicular inflammation associated with subfertility and infertility.
Topics: Angiogenesis Inhibitors; Animals; Autoimmune Diseases; Bevacizumab; Disease Models, Animal; Endothelial Cells; Leydig Cells; Macrophages; Male; Myocytes, Smooth Muscle; Neovascularization, Pathologic; Orchitis; Quail; Rats, Wistar; Signal Transduction; Testis; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2; Rats
PubMed: 33313783
DOI: 10.1093/molehr/gaaa073 -
International Journal of Surgery Case... Jun 2021Acute scrotum is considered a urological emergency requiring early intervention depending on the cause. There are multiple causes of acute scrotum with testicular...
INTRODUCTION AND IMPORTANCE
Acute scrotum is considered a urological emergency requiring early intervention depending on the cause. There are multiple causes of acute scrotum with testicular torsion being the most feared as delayed treatment leads to testicular loss. However, differentiating between epididymo-orchitis and torsion can be very difficult.
CASE PRESENTATION
We present a case of an 18-year old male patient with 2 separate episodes of acute scrotum. He had epididymo-orchitis as the first presentation followed by testicular torsion 5 days later. To our knowledge this is the first case of testicular torsion secondary to epididymo-orchitis.
CLINICAL DISCUSSION
Differentiating between epididymo-orchitis and torsion is challenging but important due to risk of loss of testis with a wrong diagnosis. Once you establish epididymo-orchitis the suspicion for subsequent torsion should be high with close follow up and adequate counselling.
CONCLUSION
He ultimately had orchiectomy, although a rare presentation, enlarged testis due to epididymo-orchitis can predispose an individual to developing testicular torsion thus adequate counselling on warning signs to patients with epididymo-orchitis is of particular importance so as to intervene early and ultimately save the testis.
PubMed: 34062357
DOI: 10.1016/j.ijscr.2021.106038 -
Human Reproduction Update Jul 2018Infection and inflammation of the reproductive tract are significant causes of male factor infertility. Ascending infections caused by sexually transmitted bacteria or... (Review)
Review
BACKGROUND
Infection and inflammation of the reproductive tract are significant causes of male factor infertility. Ascending infections caused by sexually transmitted bacteria or urinary tract pathogens represent the most frequent aetiology of epididymo-orchitis, but viral, haematogenous dissemination is also a contributory factor. Limitations in adequate diagnosis and therapy reflect an obvious need for further understanding of human epididymal and testicular immunopathologies and their contribution to infertility. A major obstacle for advancing our knowledge is the limited access to suitable tissue samples. Similarly, the key events in the inflammatory or autoimmune pathologies affecting human male fertility are poorly amenable to close examination. Moreover, the disease processes generally have occurred long before the patient attends the clinic for fertility assessment. In this regard, data obtained from experimental animal models and respective comparative analyses have shown promise to overcome these restrictions in humans.
OBJECTIVE AND RATIONALE
This narrative review will focus on male fertility disturbances caused by infection and inflammation, and the usefulness of the most frequently applied animal models to study these conditions.
SEARCH METHODS
An extensive search in Medline database was performed without restrictions until January 2018 using the following search terms: 'infection' and/or 'inflammation' and 'testis' and/or 'epididymis', 'infection' and/or 'inflammation' and 'male genital tract', 'male infertility', 'orchitis', 'epididymitis', 'experimental autoimmune' and 'orchitis' or 'epididymitis' or 'epididymo-orchitis', antisperm antibodies', 'vasectomy'. In addition to that, reference lists of primary and review articles were reviewed for additional publications independently by each author. Selected articles were verified by each two separate authors and discrepancies discussed within the team.
OUTCOMES
There is clear evidence that models mimicking testicular and/or epididymal inflammation and infection have been instructive in a better understanding of the mechanisms of disease initiation and progression. In this regard, rodent models of acute bacterial epididymitis best reflect the clinical situation in terms of mimicking the infection pathway, pathogens selected and the damage, such as fibrotic transformation, observed. Similarly, animal models of acute testicular and epididymal inflammation using lipopolysaccharides show impairment of reproduction, endocrine function and histological tissue architecture, also seen in men. Autoimmune responses can be studied in models of experimental autoimmune orchitis (EAO) and vasectomy. In particular, the early stages of EAO development showing inflammatory responses in the form of peritubular lymphocytic infiltrates, thickening of the lamina propria of affected tubules, production of autoantibodies against testicular antigens or secretion of pro-inflammatory mediators, replicate observations in testicular sperm extraction samples of patients with 'mixed atrophy' of spermatogenesis. Vasectomy, in the form of sperm antibodies and chronic inflammation, can also be studied in animal models, providing valuable insights into the human response.
WIDER IMPLICATIONS
This is the first comprehensive review of rodent models of both infectious and autoimmune disease of testis/epididymis, and their clinical implications, i.e. their importance in understanding male infertility related to infectious and non-infectious/autoimmune disease of the reproductive organs.
Topics: Animals; Autoimmune Diseases; Disease Models, Animal; Humans; Infections; Infertility, Male; Inflammation; Male; Orchitis; Rodentia
PubMed: 29648649
DOI: 10.1093/humupd/dmy009 -
Journal of Leukocyte Biology Oct 2018Testicular macrophages (TM) comprise the largest immune cell population in the mammalian testis. They are characterized by a subdued proinflammatory response upon... (Review)
Review
Testicular macrophages (TM) comprise the largest immune cell population in the mammalian testis. They are characterized by a subdued proinflammatory response upon adequate stimulation, and a polarization toward the immunoregulatory and immunotolerant M2 phenotype. This enables them to play a relevant role in supporting the archetypical functions of the testis, namely spermatogenesis and steroidogenesis. During infection, the characteristic blunted immune response of TM reflects the need for a delicate balance between a sufficiently strong reaction to counteract invading pathogens, and the prevention of excessive proinflammatory cytokine levels with the potential to disturb or destroy spermatogenesis. Local microenvironmental factors that determine the special phenotype of TM have just begun to be unraveled, and are discussed in this review.
Topics: Animals; Antigens, CD; Blood-Testis Barrier; Cellular Microenvironment; Corticosterone; Cytokines; Humans; Immune System; Immunity, Innate; Immunophenotyping; Macrophages; Male; Orchitis; Prostaglandins; Self Tolerance; Spermatogenesis; Spermatozoa; Testis; Testosterone
PubMed: 30265772
DOI: 10.1002/JLB.3MR0318-086RR -
Andrology Jan 2022Multi-organ damage is a common feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, going beyond the initially observed severe pneumonia....
BACKGROUND
Multi-organ damage is a common feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, going beyond the initially observed severe pneumonia. Evidence that the testis is also compromised is growing.
OBJECTIVE
To describe the pathological findings in testes from fatal cases of COVID-19, including the detection of viral particles and antigens, and inflammatory cell subsets.
MATERIALS AND METHODS
Postmortem testicular samples were obtained by percutaneous puncture from 11 deceased men and examined by reverse-transcription polymerase chain reaction (RT-PCR) for RNA detection and by light and electron microscopy (EM) for SARS-CoV-2. Immunohistochemistry (IHC) for the SARS-CoV-2 N-protein and lymphocytic and histiocytic markers was also performed.
RESULTS
Eight patients had mild interstitial orchitis, composed mainly of CD68+ and TCD8+ cells. Fibrin thrombi were detected in five cases. All cases presented congestion, interstitial edema, thickening of the tubular basal membrane, decreased Leydig and Sertoli cells with reduced spermatogenesis, and strong expression of vascular cell adhesion molecule (VCAM) in vessels. IHC detected SARS-Cov-2 antigen in Leydig cells, Sertoli cells, spermatogonia, and fibroblasts in all cases. EM detected viral particles in the cytoplasm of fibroblasts, endothelium, Sertoli and Leydig cells, spermatids, and epithelial cells of the rete testis in four cases, while RT-PCR detected SARS-CoV-2 RNA in three cases.
DISCUSSION AND CONCLUSION
The COVID-19-associated testicular lesion revealed a combination of orchitis, vascular changes, basal membrane thickening, Leydig and Sertoli cell scarcity, and reduced spermatogenesis associated with SARS-CoV-2 local infection that may impair hormonal function and fertility in men.
Topics: Adult; Aged; Aged, 80 and over; Autopsy; COVID-19; Humans; Male; Middle Aged; Orchitis; SARS-CoV-2; Testis
PubMed: 34196475
DOI: 10.1111/andr.13073 -
Cureus Apr 2023Emphysematous epididymo-orchitis (EEO) is a rare but serious condition that involves the presence of gas within the tissues of the testicle and/or the epididymis. It is... (Review)
Review
Emphysematous epididymo-orchitis (EEO) is a rare but serious condition that involves the presence of gas within the tissues of the testicle and/or the epididymis. It is a medical emergency that can be life-threatening if left untreated. Management of this condition may involve a combination of antibiotics, surgical drainage, and supportive care. In March 2023, A systematic review of case reports was conducted to identify and examine cases of EEO. We used PubMed, ScienceDirect, and Google Scholar for a methodical search. Only seven out of 136 studies met our criteria for this review of case reports. However, this review discusses symptom presentation, imaging findings, complications, and possible management of EEO.
PubMed: 37261165
DOI: 10.7759/cureus.38326 -
Andrologia Dec 2018In man, the wall of seminiferous tubules forms a testicular compartment, which contains several layers of smooth muscle-like, "myoid", peritubular cells and... (Review)
Review
In man, the wall of seminiferous tubules forms a testicular compartment, which contains several layers of smooth muscle-like, "myoid", peritubular cells and extracellular matrix. Its architecture and its cellular composition change in male infertility associated with impaired spermatogenesis. Increased deposits of extracellular matrix, changes in the smooth muscle-like phenotype of peritubular cells and accumulation of immune cells, especially mast cells, are among the striking alterations. Taken together, the changes indicate that inflammatory events take place in particular within this compartment. This short review summarises recent studies, which pinpoint possible mechanisms of the interplay between peritubular cells and mast cells, which may contribute to sterile inflammation and impairments of testicular function. These insights are based mainly on cellular studies, for which we used isolated human testicular peritubular cells (HTPCs), and on the examination of human testicular sections. Recent data on immunological properties of peritubular cells, unexpected roles of the extracellular matrix factor, biglycan, which is secreted by peritubular cells and functions of mast cell products (chymase, tryptase and ATP) are presented. We believe that the results may foster a better understanding of peritubular cells, their roles in the human testis and specifically their involvement in infertility.
Topics: Animals; Humans; Infertility, Male; Male; Mast Cells; Orchitis; Seminiferous Tubules; Spermatogenesis
PubMed: 30569646
DOI: 10.1111/and.13055