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1.
Andrology ; 9(1): 39-41, 2021 01.
Article in English | MEDLINE | ID: covidwho-1388168

ABSTRACT

BACKGROUND: The recent report of SARS-CoV-2 presence in semen samples of six patients, including two subjects who were recovering from the clinical disease, re-opened the discussion on possible male genital tract infection, virus shedding in semen, sexual transmission and safety of fertility treatments during the pandemic period. OBJECTIVES: To explore current data and hypothesis on the possible sites of SARS-CoV-2 infection in the male reproduction system. MATERIALS AND METHODS: We reviewed the current literature to describe: a) the evidences on angiotensin-converting enzyme 2 (AC2E) and transmembrane serine protease 2 (TMPRSS2) expression in the testes, accessory glands (including prostate) and the urinary tract; b) other coronaviruses' (SARS and MERS) ability to infect these sites. RESULTS: The co-expression of both ACE2 and TMPRSS2 genes was reported in spermatogonial stem cells, elongated spermatids, in at least a small percentage of prostate hillock cells and in renal tubular cells. Testicular damage was described in autopsies of SARS patients, without evidence of the virus in the specimens. Prostate is a known infection site for MERS-CoV. SARS-CoV-2 was detected in urines. DISCUSSION: There are still al lot of open questions on the effects of SARS-CoV-2 infection on the male reproductive tract. The presence of receptors is not a proof that the testis provides a site for viral infection and it is still unknown if SARS-CoV-2 is capable to pass the blood-testis barrier. The possibility of a prostate involvement has not been investigated yet: we have no data, but theoretically it cannot be excluded. Moreover, the RNA detected in semen could have been just a residual of urinary shedding. CONCLUSION: Opening our prospective beyond the testis could be the key to better understand the possibility of a semen-related viral transmission as well as COVID19 short and long-term effects on male reproductive function.


Subject(s)
COVID-19/virology , SARS-CoV-2/isolation & purification , Semen/virology , Testis/virology , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/diagnosis , COVID-19/metabolism , COVID-19/transmission , Humans , Male , Receptors, Virus/metabolism , Serine Endopeptidases/metabolism , Testis/metabolism , Testis/pathology , Virus Internalization , Virus Shedding
2.
Inflamm Res ; 70(10-12): 1165-1175, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1372784

ABSTRACT

OBJECTIVE: Junctional proteins are the most important component of the blood-testis barrier and maintaining the integrity of this barrier is essential for spermatogenesis and male fertility. The present study elucidated the effect of SARS-CoV-2 infection on the blood-testis barrier (BTB) in patients who died from severe acute respiratory syndrome coronavirus 2 (COVID-19) complications. METHODS: In this study, lung and testis tissue was collected from autopsies of COVID-19 positive (n = 10) and negative men (n = 10) and was taken for stereology, immunocytochemistry, and RNA extraction. RESULTS: Evaluation of the lung tissue showed that the SARS-CoV-2 infection caused extensive damage to the lung tissue and also increases inflammation in testicular tissue and destruction of the testicular blood barrier. Autopsied testicular specimens of COVID-19 showed that COVID-19 infection significantly changes the spatial arrangement of testicular cells and notably decreased the number of Sertoli cells. Moreover, the immunohistochemistry results showed a significant reduction in the protein expression of occluding, claudin-11, and connexin-43 in the COVID-19 group. In addition, we also observed a remarkable enhancement in protein expression of CD68 in the testes of the COVID-19 group in comparison with the control group. Furthermore, the result showed that the expression of TNF-α, IL1ß, and IL6 was significantly increased in COVID-19 cases as well as the expression of occludin, claudin-11, and connexin-43 was decreased in COVID-19 cases. CONCLUSIONS: Overall, the present study demonstrated that SARS-CoV-2 could induce the up-regulation of the pro-inflammatory cytokine and down-regulation of junctional proteins of the BTB, which can disrupt BTB and ultimately impair spermatogenesis.


Subject(s)
Blood-Testis Barrier/pathology , COVID-19/pathology , Cytokines/metabolism , Autopsy , Claudins/metabolism , Connexin 43/metabolism , Humans , Immunohistochemistry , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Lung/pathology , Male , Middle Aged , Occludin/metabolism , RNA, Viral/analysis , Sertoli Cells/pathology , Testis/pathology , Tumor Necrosis Factor-alpha/metabolism
3.
Immunity ; 54(9): 2143-2158.e15, 2021 09 14.
Article in English | MEDLINE | ID: covidwho-1364125

ABSTRACT

Neutralizing antibodies (NAbs) are effective in treating COVID-19, but the mechanism of immune protection is not fully understood. Here, we applied live bioluminescence imaging (BLI) to monitor the real-time effects of NAb treatment during prophylaxis and therapy of K18-hACE2 mice intranasally infected with SARS-CoV-2-nanoluciferase. Real-time imaging revealed that the virus spread sequentially from the nasal cavity to the lungs in mice and thereafter systemically to various organs including the brain, culminating in death. Highly potent NAbs from a COVID-19 convalescent subject prevented, and also effectively resolved, established infection when administered within three days. In addition to direct neutralization, depletion studies indicated that Fc effector interactions of NAbs with monocytes, neutrophils, and natural killer cells were required to effectively dampen inflammatory responses and limit immunopathology. Our study highlights that both Fab and Fc effector functions of NAbs are essential for optimal in vivo efficacy against SARS-CoV-2.


Subject(s)
Antibodies, Neutralizing/metabolism , Antibodies, Viral/metabolism , Brain/pathology , COVID-19/immunology , Lung/pathology , SARS-CoV-2/physiology , Testis/pathology , Angiotensin-Converting Enzyme 2/genetics , Animals , Antibodies, Neutralizing/genetics , Antibodies, Viral/genetics , Brain/virology , COVID-19/therapy , Cells, Cultured , Disease Models, Animal , Humans , Immunoglobulin Fc Fragments/genetics , Luciferases/genetics , Luminescent Measurements , Lung/virology , Male , Mice , Mice, Transgenic , Testis/virology
4.
Cells ; 10(6)2021 06 12.
Article in English | MEDLINE | ID: covidwho-1270010

ABSTRACT

Coronavirus disease 2019 (COVID-19), a global pandemic, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV-2 and transmembrane serine protease 2 (TMPRSS2) facilitates ACE2-mediated virus entry. Moreover, the expression of ACE2 in the testes of infertile men is higher than normal, which indicates that infertile men may be susceptible to be infected and SARS-CoV-2 may cause reproductive disorder through the pathway induced by ACE2 and TMPRSS2. Little is known about the pathway regulation of ACE2 and TMPRSS2 expression in male reproductive disorder. Since the regulation of gene expression is mediated by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) at the post-transcriptional level, the aim of this study was to analyze the dysregulated miRNA-lncRNA interactions of ACE2 and TMPRSS2 in male reproductive disorder. Using bioinformatics analysis, we speculate that the predicted miRNAs including miR-125a-5p, miR-125b-5p, miR-574-5p, and miR-936 as regulators of ACE2 and miR-204-5p as a modulator of TMPRSS2 are associated with male infertility. The lncRNAs with a tissue-specific expression for testis including GRM7-AS3, ARHGAP26-AS1, BSN-AS1, KRBOX1-AS1, CACNA1C-IT3, AC012361.1, FGF14-IT1, AC012494.1, and GS1-24F4.2 were predicted. The identified miRNAs and lncRNAs are proposed as potential biomarkers to study the possible association between COVID-19 and male infertility. This study encourages further studies of miRNA-lncRNA interactions to explain the molecular mechanisms of male infertility in COVID-19 patients.


Subject(s)
COVID-19/complications , Gene Regulatory Networks , Infertility, Male/virology , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Adult , Angiotensin-Converting Enzyme 2/physiology , COVID-19/genetics , Computational Biology/methods , Computer Simulation , Gene-Environment Interaction , Humans , Infertility, Male/genetics , Male , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , SARS-CoV-2/physiology , Serine Endopeptidases/physiology , Testis/metabolism , Testis/pathology , Testis/virology , Virus Internalization
5.
Front Endocrinol (Lausanne) ; 12: 677701, 2021.
Article in English | MEDLINE | ID: covidwho-1268244

ABSTRACT

Background: Angiotensin-converting enzyme II (ACE2), a receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) to enter host cells, is widely expressed in testes and prostate tissues. The testis and prostate produce semen. At present, there are contradictory reports about whether SARS-CoV-2 can exist in the semen of infected men. Objective: To provide a comprehensive overview of the topic of whether COVID-19 can impact on male reproductive system. Methods: We reviewed the relevant publications on the possible impact of Coronavirus Disease 2019 (COVID-19) on male reproductive system and summarized the latest and most important research results so far. Literature published in English from December 2019 to January 31, 2021 regarding the existence of SARS-CoV-2 in semen, testis, and prostatic fluid and the effects of COVID-19 on male reproductive were included. Results: We identified 28 related studies, only one of which reported the presence of SARS-CoV-2 in semen. The study found that the semen quality of patients with moderate infection was lower than that of patients with mild infection and healthy controls. The impaired semen quality may be related to fever and inflammation. Pathological analysis of the testis/epididymis showed that SARS-CoV-2 viral particles were positive in 10 testicular samples, and the spermatogenic function of the testis was impaired. All 94 expressed prostatic secretion (EPS) samples were negative for SARS-CoV-2 RNA. Conclusion: The likelihood of SARS-CoV-2 in the semen of COVID-19 patients is very small, and semen should rarely be regarded as a carrier of SARS-CoV-2 genetic material. However, COVID-19 may cause testicular spermatogenic dysfunction via immune or inflammatory reactions. Long-term follow-up is needed for COVID-19 male patients and fetuses conceived during the father's infection period.


Subject(s)
COVID-19/physiopathology , Genitalia, Male/virology , SARS-CoV-2/physiology , COVID-19/complications , COVID-19/pathology , Genitalia, Male/pathology , Genitalia, Male/physiology , History, 21st Century , Humans , Inflammation/complications , Inflammation/pathology , Inflammation/virology , Male , Prostate/pathology , Prostate/physiology , Prostate/virology , Semen/virology , Semen Analysis , Sexual Dysfunction, Physiological/pathology , Sexual Dysfunction, Physiological/virology , Testis/pathology , Testis/physiology , Testis/virology
6.
J Med Virol ; 93(3): 1396-1402, 2021 03.
Article in English | MEDLINE | ID: covidwho-1196517

ABSTRACT

The outbreak of novel coronavirus disease 2019 (COVID-19) has become a major pandemic threat worldwide. According to the existing clinical data, this virus not only causes respiratory diseases and affects the lungs but also induces histopathological or functional changes in various organs like the testis and also the male genital tract. The renin-angiotensin system (RAS), also ACE 2 and TMPRSS2 play an important role in the cellular entry for SARS-CoV-2. Because the male genital system presents high ACE 2 expression, the importance of this pathway increases in COVID-19 cases. As the COVID-19 pandemic has affected the male genital system in direct or indirect ways and showed a negative impact on male reproduction, this paper focuses on the possible mechanisms underlying the damage caused by COVID-19 to the testis and also other components of the male genital tract.


Subject(s)
COVID-19/physiopathology , Fertility , Infertility, Male/etiology , SARS-CoV-2/physiology , Angiotensin-Converting Enzyme 2/metabolism , Brain/physiopathology , COVID-19/complications , COVID-19/pathology , COVID-19/virology , Epididymis/pathology , Genitalia, Male/pathology , Genitalia, Male/virology , Humans , Infertility, Male/physiopathology , Infertility, Male/virology , Male , Receptors, Coronavirus/metabolism , SARS-CoV-2/pathogenicity , Testis/pathology
7.
Biochemistry (Mosc) ; 86(4): 389-396, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1150206

ABSTRACT

The novel coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major public health emergency worldwide with over 118.27-million confirmed COVID-19 cases and 2.62-million deaths recorded, as of March 12, 2021. Although this disease primarily targets lungs, damages in other organs, such as heart, kidney, liver, and testis, may occur. Testis is the cornerstone of male reproduction, while reproductive health is the most valuable resource for continuity of the human race. Given the unique nature of SARS-CoV-2, the mechanisms of its impact on the testes have yet to be fully explored. Notably, coronaviruses have been found to invade target cells through the angiotensin-converting enzyme 2 receptor, which can be found in the respiratory, gastrointestinal, cardiovascular, urinary tract, and reproductive organs, such as testes. Coronavirus studies have suggested that testes might be a potential target for SARS-CoV-2 infection. The first etiopathogenic concept proposed by current hypotheses indicates that the virus can invade testes through the angiotensin-converting enzyme 2 receptor. Next, the activated inflammatory response in the testes, disease-associated fever, and COVID-19 medications might be implicated in testicular alterations. Although evidence regarding the presence of SARS-CoV-2 mRNA in semen remains controversial, this emphasizes the need for researchers to pay closer attention to sexually transmitted diseases and male fertility after recovering from COVID-19. In this review the latest updates regarding COVID-19-associated testicular dysfunction are summarized and possible pathogenic mechanisms are discussed.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Fertility , Pandemics , SARS-CoV-2/metabolism , Testis/metabolism , COVID-19/mortality , COVID-19/pathology , Humans , Male , Testis/pathology , Testis/virology
8.
Andrology ; 9(4): 1027-1037, 2021 07.
Article in English | MEDLINE | ID: covidwho-1066607

ABSTRACT

BACKGROUND: The testes are suspected target organs of SARS-CoV-2. However, the results of studies on the effect of COVID-19 on male reproduction are controversial. OBJECTIVE: To summarize current research on the effects of COVID-19 on male reproduction. METHODS: A systematic review of English literature was performed using PubMed and Ovid Embase up to 18 August 2020. Research articles on the presence of SARS-CoV-2 in semen, the effects of the virus on semen parameters and any pathological changes in the testes were evaluated. RESULTS: Fourteen studies were included in this review. Six of 176 survivors (3.4%) and 1 of 13 decedents (7.7%) in 2 of 12 studies were positive for viral RNA in semen and testicular tissue, respectively. After stratification of patient groups, we found that the virus was detected in the relatively early stage of infection, 6-16 days after disease onset, in semen from survivors. Two of 3 studies reported that some participants had substandard semen quality after COVID-19, and 1 study found that COVID-19 may impair semen quality in a severity-related manner. Pathological analyses showed that injuries to the seminiferous tubule occurred in all decedents (N = 11). Another study found that orchitic and testis fibrin microthrombi occurred in patients with fatal disease (100%, N = 2). Scrotal discomfort of orchiepididymitis or spermatic cord inflammation has also been reported in COVID-19 patients. CONCLUSION: Current studies suggest that semen is rarely considered a carrier of SARS-CoV-2 genetic material during the infection period but not in the semen of recovered patients. Fatal COVID-19 may cause testicular structure damage without the presence of virus.


Subject(s)
COVID-19/physiopathology , Reproduction , Semen/virology , COVID-19/pathology , COVID-19/virology , Humans , Male , Semen Analysis , Seminiferous Tubules/pathology , Seminiferous Tubules/virology , Testis/pathology , Testis/virology
10.
Reprod Sci ; 28(10): 2735-2742, 2021 10.
Article in English | MEDLINE | ID: covidwho-1014275

ABSTRACT

Coronavirus disease 2019 (COVID-19), which resulted from the pandemic outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a massive inflammatory cytokine storm leading to multi-organ damage including that of the brain and testes. While the lungs, heart, and brain are identified as the main targets of SARS-CoV-2-mediated pathogenesis, reports on its testicular infections have been a subject of debate. The brain and testes are physiologically synchronized by the action of gonadotropins and sex steroid hormones. Though the evidence for the presence of the viral particles in the testicular biopsies and semen samples from COVID-19 patients are highly limited, the occurrence of testicular pathology due to abrupt inflammatory responses and hyperthermia has incresingly been evident. The reduced level of testosterone production in COVID-19 is associated with altered secretion of gonadotropins. Moreover, hypothalamic pathology which results from SARS-CoV-2 infection of the brain is also evident in COVID-19 cases. This article revisits and supports the key reports on testicular abnormalities and pathological signatures in the hypothalamus of COVID-19 patients and emphasizes that testicular pathology resulting from inflammation and oxidative stress might lead to infertility in a significant portion of COVID-19 survivors. Further investigations are required to monitor the reproductive health parameters and HPG axis abnormalities related to secondary pathological complications in COVID-19 patients and survivors.


Subject(s)
COVID-19/epidemiology , Fertility , Hypothalamus/pathology , Infertility, Male/epidemiology , SARS-CoV-2/pathogenicity , Testis/pathology , Animals , Atrophy , COVID-19/diagnosis , COVID-19/virology , Gonadotropins/metabolism , Host-Pathogen Interactions , Humans , Hypothalamo-Hypophyseal System/metabolism , Hypothalamo-Hypophyseal System/pathology , Hypothalamo-Hypophyseal System/physiopathology , Hypothalamo-Hypophyseal System/virology , Hypothalamus/metabolism , Hypothalamus/physiopathology , Hypothalamus/virology , Incidence , Infertility, Male/pathology , Infertility, Male/physiopathology , Infertility, Male/virology , Male , Testis/metabolism , Testis/physiopathology , Testis/virology , Testosterone/metabolism
13.
Reprod Toxicol ; 99: 65-70, 2021 01.
Article in English | MEDLINE | ID: covidwho-943568

ABSTRACT

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.


Subject(s)
COVID-19/complications , Fertility/immunology , Infertility, Male/etiology , SARS-CoV-2/isolation & purification , COVID-19/immunology , COVID-19/pathology , Humans , Infertility, Male/pathology , Infertility, Male/virology , Male , Spermatogenesis/immunology , Spermatozoa/pathology , Spermatozoa/virology , Testis/pathology , Testis/virology
14.
Rev Int Androl ; 18(3): 117-123, 2020.
Article in Spanish | MEDLINE | ID: covidwho-826748

ABSTRACT

OBJECTIVE: The main objective of this revision is to summarize the current existing evidence of the potential adverse effects of SARS-CoV-2 on the male reproductive system and provide the recommendations of the Asociación Española de Andrología, Medicina Sexual y Reproductiva (ASESA) concerning the implications of COVID-19 infection in the management of male infertilty patients and testicular endocrine dysfunction. METHODS: A comprehensive systematic literature search of the databases of PubMed, Web of Science, Embase, Medline, Cochrane and MedRxiv, was carried out. RESULTS: The presence of orchitis as a potential complication of the infection by SARS-CoV-2 has not yet been confirmed. One study reported that 19% of males with COVID-19 infection had scrotal symptoms suggestive of viral orchitis which could not be confirmed. It is possible that the virus, rather than infecting the testes directly, may induce a secondary autoimmune response leading to autoimmune orchitis. COVID-19 has been associated with coagulation disorders and thus the orchitis could be the result of segmental vasculitis. Existing data concerning the presence of the virus in semen are contradictory. Only one study reported the presence of RNA in 15.8% of patients with COVID-19. However, the presence of nucleic acid or antigen in semen is not synonyms of viral replication capacity and infectivity. It has been reported an increase in serum levels of LH in males with COVID-19 and a significant reduction in the T/LH and FSH/LH ratios, consistent with subclinical hypogonadism. CONCLUSIONS: The findings of recent reports related to the potential effects of COVID-19 infection on the male reproductive system are based on poorly designed, small sample size studies that provide inconclusive, contradictory results. Since there still exists a theoretical possibility of testicular damage and male infertilty as a result of the infection by COVID-19, males of reproductive age should be evaluated for gonadal function and semen analysis. With regard to the sexual transmission of the virus, there is not sufficient evidence to recommend asymptomatic couples to abstein from having sex in order to protect themselves from being infected by the virus. Additional studies are needed to understand the long-term effects of SARS-CoV-2 on male reproductive function, including male fertility potential and endocrine testicular function.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Pandemics , Pneumonia, Viral/complications , Reproductive Health , Sexual Health , Adult , Betacoronavirus/isolation & purification , Betacoronavirus/pathogenicity , Betacoronavirus/physiology , COVID-19 , Follicle Stimulating Hormone/blood , Humans , Hypogonadism/blood , Hypogonadism/etiology , Immunoglobulin G/analysis , Leukocytes , Luteinizing Hormone/blood , Male , Orchitis/etiology , Orchitis/virology , Prostate/virology , RNA, Viral/analysis , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Semen/virology , Semen Preservation , Spain , Testis/immunology , Testis/pathology , Testis/virology , Testosterone/blood , Vasculitis/etiology , Young Adult
15.
Andrologia ; 52(9): e13791, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-712969

ABSTRACT

Male infertility is linked to some viral infections including human papillomavirus (HPV), herpes simplex viruses (HSV) and human immunodeficiency viruses (HIVs). Almost nothing is known about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) effect on fertility. The possible risk factors of coronavirus disease 2019 (COVID-19) infection on fertility comes from the abundance of angiotensin-Converting Enzyme-2 (ACE2), receptor entry of the virus, on testes, a reduction in important sex hormone ratios and COVID-19-associated fever. Recent studies have shown a gender difference for COVID-19 rates and comorbidity. In this review, we will discuss the potential effect of COVID-19 on male fertility and talk about what needs to be done by the scientific community to tackle our limited understanding of the disease. On the other side, we will focus on what is known so far about the risk of COVID-19 on pregnancy, neonatal health and the vertical transfer of the virus between mothers and their neonates. Finally, because reproduction is a human right and infertility is considered a health disease, we will discuss how assisted reproductive clinics can cope with the pandemic and what guidelines they should follow to minimise the risk of viral transmission.


Subject(s)
Coronavirus Infections/complications , Infectious Disease Transmission, Vertical , Infertility, Male/virology , Pneumonia, Viral/complications , Pregnancy Complications, Infectious/virology , Reproductive Health , Angiotensin-Converting Enzyme 2 , Betacoronavirus/isolation & purification , Betacoronavirus/metabolism , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Female , HIV Infections/complications , HIV Infections/transmission , HIV Infections/virology , Herpes Simplex/complications , Herpes Simplex/transmission , Herpes Simplex/virology , Humans , Infertility, Male/pathology , Male , Pandemics , Papillomavirus Infections/complications , Papillomavirus Infections/transmission , Papillomavirus Infections/virology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Pregnancy , Risk Factors , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Testis/metabolism , Testis/pathology
16.
Reprod Biomed Online ; 41(5): 903-906, 2020 11.
Article in English | MEDLINE | ID: covidwho-664335

ABSTRACT

RESEARCH QUESTION: Can the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus induce testis damage and dysfunction? DESIGN: This is the description of the case of a young man presenting with heavy testicular pain as the first symptom of COVID-19 infection. A review of the literature is also presented. RESULTS: SARS-CoV-2 may enter into the host cell by binding to angiotensin-converting enzyme 2. This receptor seems to be widely expressed in different testicular cell types, making possible the occurrence of orchitis in male patients with COVID-19 infection. From a review of the literature, it seems that there is currently no evidence of sexual transmission of SARS-CoV-2; however, the possibility of virus-induced testis damage and dysfunction cannot be excluded. CONCLUSIONS: Further studies are necessary on the pathological effect of SARS-CoV-2 in the male reproductive system and to ensure a proper andrological follow-up for male patients.


Subject(s)
Coronavirus Infections/diagnosis , Pelvic Pain/diagnosis , Pneumonia, Viral/diagnosis , Testicular Diseases/diagnosis , Testis/virology , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Diagnosis, Differential , Humans , Male , Pandemics , Pelvic Pain/epidemiology , Pelvic Pain/etiology , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Testicular Diseases/epidemiology , Testicular Diseases/virology , Testis/pathology , Testis/physiology
17.
Reprod Sci ; 28(1): 23-26, 2021 01.
Article in English | MEDLINE | ID: covidwho-640228

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization (WHO) on 11th March 2020. Bulk of research on this virus are carried out to unveil its multivariate pathology. Surprisingly, men are reportedly more vulnerable to COVID-19 even with higher fatality rate compared to women. Thus, it is crucial to determine whether SARS-CoV-2 infection can even affect male fertility as an immediate or long-term consequence of the disease. Among the discrete data available, an important finding is that angiotensin converting enzymes 2 (ACE2) receptor, that aids the SARS-CoV-2 entry into host cells, is profoundly expressed in testicular cells. In addition, the endogenous androgen milieu and its receptors are associated with ACE2 activation reflecting that enhanced testosterone levels may trigger the pathogenesis of COVID-19. In contrary, hypogonadism has also been reported in the acute phase of some COVID-19 cases. Moreover, SARS-CoV-2 infection-induced uncontrolled inflammatory responses may lead to systemic oxidative stress (OS), whose severe disruptive effects on testicular functions are well-documented. This article aims to precisely present the possible impact of COVID-19 on male reproductive functions, and to highlight the speculations that need in-depth research for the exact underlying mechanisms how COVID-19 is associated with men's health and fertility.


Subject(s)
COVID-19/epidemiology , COVID-19/pathology , Infertility, Male/epidemiology , Infertility, Male/pathology , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Humans , Infertility, Male/metabolism , Male , SARS-CoV-2/metabolism , Testis/metabolism , Testis/pathology
18.
Eur J Clin Microbiol Infect Dis ; 39(12): 2447-2455, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-622381

ABSTRACT

This study compared the laboratory indexes in 40 non-severe COVID-19 patients with those in 57 healthy controls. In the peripheral blood system of non-severe symptom COVID-19 patients, lymphocytes, eosinophils, basophils, total procollagen type 1 amino-terminal propeptide, osteocalcin N-terminal, thyroid-stimulating hormone, growth hormone, and insulin-like growth factor-binding protein 3 significantly decreased, and total protein, albumin, alanine transaminase, alkaline phosphatase, γ-glutamyl transferase, activated partial thromboplastin time, prothrombin time, fibrinogen, D-dimer, fibrinogen degradation products, human epididymal protein 4, serum ferritin, and C-reactive protein were elevated. SARS-CoV-2 infection can affect hematopoiesis, hemostasis, coagulation, fibrinolysis, bone metabolism, thyroid, parathyroid glands, the liver, and the reproductive system.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Adult , Biomarkers/blood , Bone and Bones/metabolism , Bone and Bones/pathology , Bone and Bones/virology , C-Reactive Protein/metabolism , COVID-19 , Case-Control Studies , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Cross-Sectional Studies , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinolysis , Hematopoiesis , Hemostasis , Humans , Liver/metabolism , Liver/pathology , Liver/virology , Male , Middle Aged , Ovary/metabolism , Ovary/pathology , Ovary/virology , Parathyroid Glands/metabolism , Parathyroid Glands/pathology , Parathyroid Glands/virology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , SARS-CoV-2 , Serum Albumin/metabolism , Severity of Illness Index , Testis/metabolism , Testis/pathology , Testis/virology , Thyroid Gland/metabolism , Thyroid Gland/pathology , Thyroid Gland/virology
19.
Andrologia ; 52(9): e13712, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-613270

ABSTRACT

We performed this systematic review to evaluate the possibility of an impact of SARS-CoV-2 infection on male fertility. SARS-CoV-2 enters the cells with the help of ACE2; therefore, testicular expression of ACE2 was analysed from transcriptome sequencing studies and our unpublished data. Literature suggested that SARS-CoV-1 (2002-2004 SARS) had a significant adverse impact on testicular architecture, suggesting a high possibility of the impact of SARS-CoV-2 as well. Out of two studies on semen samples from COVID-19 affected patients, one reported the presence of SARS-CoV-2 in the semen samples while the other denied it, raising conflict about its presence in the semen samples and the possibility of sexual transmission. Our transcriptome sequencing studies on rat testicular germ cells showed ACE expression in rat testicular germ cells. We also found ACE2 expression in transcriptome sequencing data for human spermatozoa, corroborating its presence in the testicular germ cells. Transcriptome sequencing data from literature search revealed ACE2 expression in the germ, Sertoli and Leydig cells. The presence of ACE2 on almost all testicular cells and the report of a significant impact of previous SARS coronavirus on testes suggest that SARS-CoV-2 is highly likely to affect testicular tissue, semen parameters and male fertility.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/complications , Infertility, Male/virology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/complications , Testis/metabolism , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/metabolism , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Gene Expression Profiling , Humans , Infertility, Male/pathology , Male , Models, Animal , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Rats , SARS-CoV-2 , Semen/virology , Spermatozoa/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Testis/pathology
20.
Eur Urol Focus ; 6(5): 1124-1129, 2020 Sep 15.
Article in English | MEDLINE | ID: covidwho-437089

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), involves multiple organs. Testicular involvement is largely unknown. OBJECTIVE: To determine the pathological changes and whether SARS-CoV-2 can be detected in the testes of deceased COVID-19 patients. DESIGN, SETTING, AND PARTICIPANTS: Postmortem examination of the testes from 12 COVID-19 patients was performed using light and electron microscopy, and immunohistochemistry for lymphocytic and histiocytic markers. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the virus in testicular tissue. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Seminiferous tubular injury was assessed as none, mild, moderate, or severe according to the extent of tubular damage. Leydig cells in the interstitium were counted in ten 400× microscopy fields. RESULTS AND LIMITATIONS: Microscopically, Sertoli cells showed swelling, vacuolation and cytoplasmic rarefaction, detachment from tubular basement membranes, and loss and sloughing into lumens of the intratubular cell mass. Two, five, and four of 11 cases showed mild, moderate, and severe injury, respectively. The mean number of Leydig cells in COVID-19 testes was significantly lower than in the control group (2.2 vs 7.8, p < 0.001). In the interstitium there was edema and mild inflammatory infiltrates composed of T lymphocytes and histiocytes. Transmission EM did not identify viral particles in three cases. RT-PCR detected the virus in one of 12 cases. CONCLUSIONS: Testes from COVID-19 patients exhibited significant seminiferous tubular injury, reduced Leydig cells, and mild lymphocytic inflammation. We found no evidence of SARS-CoV-2 virus in the testes in the majority (90%) of the cases by RT-PCR, and in none by electron microscopy. These findings can provide evidence-based guidance for sperm donation and inform management strategies to mitigate the risk of testicular injury during the COVID-19 disease course. PATIENT SUMMARY: We examined the testes of deceased COVID-19 patients. We found significant damage to the testicular parenchyma. However, virus was not detected in testes in the majority of cases.


Subject(s)
Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Seminiferous Tubules/pathology , Testis/pathology , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2 , Betacoronavirus , COVID-19 , Cell Count , Coronavirus Infections/metabolism , Coronavirus Infections/physiopathology , Humans , Inflammation , Leydig Cells/pathology , Leydig Cells/ultrastructure , Male , Microscopy, Electron , Middle Aged , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/metabolism , Pneumonia, Viral/physiopathology , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Seminiferous Tubules/ultrastructure , Sertoli Cells/pathology , Sertoli Cells/ultrastructure , Spermatogenesis/physiology , Testis/metabolism , Testis/ultrastructure , Testis/virology
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