Impact of SARS-CoV-2 Infection on the Male Reproductive Tract: Potential Consequences and Pathological Findings

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), is an enveloped positive-sense, single-stranded RNA virus that can cause disease primarily affecting the respiratory tract. However, SARS-CoV-2 has also been shown to infect the male reproductive tract (MRT), and there is growing evidence that this infection can have short- and long-term implications for male fertility.

How SARS-CoV-2 Infects the MRT

The receptor angiotensin-converting enzyme 2 (ACE2), in addition to serine protease, transmembrane protease serine 2 (TMPRSS2), can promote SARS-CoV-2 entry through cleavage of its spike glycoprotein, (S) protein, which allows for fusion of the cell membrane. ACE2 is primarily expressed in the cell lining of the alveoli as well as the male reproductive tract on the spermatogonia, Sertoli cells in seminiferous tubules, and Leydig cells

SARS-CoV-2 Infection of the Male Reproductive Tract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), is an enveloped positive-sense, single-stranded RNA virus that can cause disease primarily affecting the respiratory tract. However, SARS-CoV-2 has also been shown to infect the male reproductive tract (MRT), and there is growing evidence that this infection can have short- and long-term implications for male fertility.

How SARS-CoV-2 Infects the MRT

The receptor angiotensin-converting enzyme 2 (ACE2), in addition to serine protease, transmembrane protease serine 2 (TMPRSS2), can promote SARS-CoV-2 entry through cleavage of its spike glycoprotein, (S) protein, which allows for fusion of the cell membrane. ACE2 is primarily expressed in the cell lining of the alveoli as well as the male reproductive tract on the spermatogonia, Sertoli cells in seminiferous tubules, and Leydig cells. This could account, in part, for why men are more impacted than females, with higher rates of mortality and greater severity of disease. Studies indicate SARS-CoV-2 attachment to ACE2 facilitates the infection in the male reproductive tract.

Pathological Changes in the MRT

Studies have shown that SARS-CoV-2 infection of the MRT can lead to a number of pathological changes, including:

  • Damage to seminiferous tubules
  • Reduction of Leydig cells
  • Reduced spermatogenesis
  • Lymphocytic inflammation
  • Thickening of the testicular tunica propria
  • Signs of orchitis

These changes can lead to a number of problems, including:

  • Low sperm count
  • Poor sperm motility
  • Abnormal sperm morphology
  • Infertility

Long-Term Implications

The long-term implications of SARS-CoV-2 infection of the MRT are not yet fully understood. However, some studies have suggested that the infection may lead to permanent damage to the testes, which could have a lasting impact on male fertility. More research is needed to better understand the long-term effects of SARS-CoV-2 infection on the MRT.

Pathological Changes in the MRT

Studies have shown that SARS-CoV-2 infection of the MRT can lead to a number of pathological changes, including:

  • Damage to seminiferous tubules
  • Reduction of Leydig cells
  • Reduced spermatogenesis
  • Lymphocytic inflammation
  • Thickening of the testicular tunica propria
  • Signs of orchitis

These changes can lead to a number of problems, including:

  • Low sperm count
  • Poor sperm motility
  • Abnormal sperm morphology
  • Infertility

Long-Term Implications

The long-term implications of SARS-CoV-2 infection of the MRT are not yet fully understood. However, some studies have suggested that the infection may lead to permanent damage to the testes, which could have a lasting impact on male fertility. More research is needed to better understand the long-term effects of SARS-CoV-2 infection on the MRT.

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), primarily affects the respiratory system. However, emerging evidence suggests that SARS-CoV-2 can cause systemic infections, affecting various organs and tissues beyond the respiratory tract. This article aims to explore the impact of SARS-CoV-2 on the male reproductive tract (MRT) and its potential consequences.

SARS-CoV-2 Infection and Extrapulmonary Complications

Autopsy studies have revealed widespread viral replication in both respiratory and non-respiratory tissues in severe COVID-19 cases. The presence of viral antigens in immune cell populations suggests that SARS-CoV-2 can potentially infect a broad range of target cells. Studies have detected SARS-CoV-2 infection in organs such as the heart, brain, gastrointestinal tract, kidneys, liver, and the MRT. These findings highlight that SARS-CoV-2 is not limited to the respiratory system and can cause systemic infections.

Testicular Infection by SARS-CoV-2

The receptor angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) promote SARS-CoV-2 entry into human cells. ACE2 is abundantly expressed in the cells of the MRT, including spermatogonia, Sertoli cells, and Leydig cells. This may explain why men are more severely impacted by COVID-19 compared to females. Studies indicate that SARS-CoV-2 can attach to ACE2 receptors in the MRT, leading to testicular infection.

Comorbidities and Testicular Disease

Comorbidities such as diabetes, obesity, hypertension, and cardiovascular disease can increase the risk of severe illness and histopathological damage in COVID-19 patients. These comorbidities may also impact male reproductive health, including testosterone levels, testicular dysfunction, and inflammation. Diabetes and obesity, in particular, are associated with lowered testosterone levels and testicular damage. The interaction between COVID-19 and pre-existing diseases may augment inflammation and render individuals more vulnerable to testicular damage.

Pathological Findings and Testicular Damage

The testes are considered an immune-privileged organ, protected by the blood-testes barrier (BTB). However, SARS-CoV-2 infection can disrupt the BTB and lead to testicular damage. Studies have shown pathological changes in testicular tissue, such as impairments of spermatogenesis, lymphocyte infiltration, thickening of the seminiferous tubules, and damage to the tunica propria.

COVID-19 patients have also exhibited decreased testosterone levels, testicular pain, erectile dysfunction, and abnormalities in semen parameters. These findings suggest that SARS-CoV-2 infection can cause testicular damage and affect fertility.

Role of the Local Immune Response

The testicular immune response plays a crucial role in countering viral infections. Testicular inflammatory damage resulting from COVID-19 may be an indirect result of the immune system’s efforts to eliminate the virus. Mast cells, lymphocyte infiltration, and elevated cytokine levels have been observed in the testes of COVID-19 patients. These immune responses can potentially lead to testicular damage, disruption of spermatogenesis, and impaired testosterone production.

Conclusion

SARS-CoV-2 infection can have short and long-term implications for the male reproductive tract. It can cause testicular infection, disrupt the BTB, and lead to testicular damage, impairments of spermatogenesis, and hormonal imbalances. COVID-19 may also impact male fertility and sexual function. The interaction between SARS-CoV-2 and comorbidities, such as diabetes and obesity, may further exacerbate testicular damage and inflammation.

Further research is needed to fully understand the long-term consequences of SARS-CoV-2 infection on male reproductive health. Studies exploring the persistence of viral particles in the testes, the duration and extent of testicular damage, and the recovery of reproductive function are crucial to provide comprehensive insights into the impact of COVID-19 on male fertility.

In conclusion, SARS-CoV-2 infection has the potential to affect the male reproductive tract and fertility. Testicular infection, disruption of the blood-testes barrier, and testicular damage have been observed in COVID-19 patients. Understanding the mechanisms underlying these effects is essential for developing strategies to mitigate the impact of the virus on male reproductive health. Additionally, individuals with pre-existing comorbidities should be particularly mindful of their reproductive health and seek appropriate medical guidance during and after COVID-19 infection.

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