Impact of SARS-CoV-2 infection on human sperm quality

Corona disease 2019 (COVID-19) pandemic outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to an unexpected global health crisis. It has adversely affected the health systems of various countries and the renovation of medical procedures and protocols to curb the effects of the pandemic. These renovations include protocols and procedures in andrology laboratories to avoid adversely affecting the performance of assisted reproduction technologies.

Study: Human sperm quality affected by SARS-CoV-2 infection: An updated review.  Image credit: Cinemanikor / ShutterstockExamination: Human sperm quality affected by SARS-CoV-2 infection: An updated review. Image credit: Cinemanikor / Shutterstock

The effect of SARS-CoV-2 infection on sperm quality and sperm parameters, which in turn reflect sperm quality and quantity, is of great importance to healthcare providers and researchers worldwide. To date, more than 50 articles have been published in PubMed and Scopus databases linking sperm-quality SARS-CoV-2 infection.

A new review article published in Andrology was intended to extract, review and summarize these articles from the mentioned databases in order to determine the association between SARS-CoV-2 infection and sperm quality.

Presence of SARS-CoV-2 in human semen

The angiotensin-converting enzyme 2 (ACE-2) receptor is responsible for the virus’ entry into the cell and infection. In addition to the lungs, ACE-2 has also been detected in the testes. Therefore, testicles and semen may be potential targets for SARS-CoV-2.

The presence of SARS-CoV-2 in semen can adversely affect sperm parameters and lead to male infertility. In addition, it can have consequences for sexually transmitted infections, congenital disease, embryonic infection and miscarriage.

Recent studies conducted in different countries indicated that the presence of SARS-CoV-2 was not detected in semen and no transmission of SARS-CoV-2 was observed under assisted reproduction technology.

Effect of SARS-CoV-2 infection on human sperm parameters

Currently, seven studies have been performed to determine the effect of SARS-CoV-2 infection on sperm parameters. Most of these studies were observational. In most of these studies, sperm quality was analyzed during the recovery stage of the infection using RT-PCR.

The results showed that out of the seven studies, six revealed a negative impact of SARS-CoV-2 infection on sperm parameters. Sperm count was found to be the most affected parameter of SARS-CoV-2 infection. However, further research is needed to provide more collective and robust information.

Effect of SARS-CoV-2 infection on gonadal hormones

Spermatogenesis in human men is controlled by gonadal hormones such as testosterone, follicle-stimulating hormone and luteinizing hormone. It turned out that the luteinizing hormone and the follicle-stimulating hormone controlled the number of Leydig cells in the testes. The Leydig cells, in turn, were responsible for the synthesis of testosterone.

It was observed that patients infected with COVID-19 had lower levels of luteinizing hormone and testosterone compared to healthy individuals. In addition, patients were found to have higher levels of luteinizing and prolactin and lower levels of total testosterone compared to controls. In addition, severe cases of COVID-19 were associated with a greater reduction in total testosterone levels.

The increase in luteinizing hormone levels and decreased testosterone: luteinizing hormone ratios can lead to testicular dysfunction that can affect spermatogenesis.

Effect of SARS-CoV-2 on testicular function

It has been shown that the entry of SARS-CoV-2 inside the cells depends on the ACE-2 receptors and transmembrane serine protease 2. However, it has been observed that transmembrane serine protease 2 is only expressed in a subpopulation of germ cells, while ACE -2 receptors are expressed in Sertoli cells. In addition, both ACE-2 and transmembrane serine protease 2 had limited expression in testicular tissue. This evidence supports that the virus is unlikely to enter the testicle.

However, a fever of 39 degrees Celsius or more for more than three days can lead to severe deterioration of sperm quality, leading to azoospermia. It has been shown that fever, even for a limited duration, can significantly reduce sperm parameters (eg number, motility and / or vitality) and alter the integrity of sperm DNA. However, as fever is a common symptom of COVID-19, fever-induced COVID-19 can alter sperm quality and reduce sperm parameters even in the absence of sperm virus and immune responses.

Effect of SARS-CoV-2 infection on the testicles

Although the testicles usually remain unaffected by the host’s response to antigens, it was found from autopsy samples of COVID-19 patients that several expressed proteins were down-regulated in testicular tissue. The expression of insulin factor-3, the most expressed protein in testicular tissue, especially Leydig cells, was found to be reduced in COVID-19 patients. This can lead to impairment of function and / or population in the Leydig cells. Another enzyme, the E3 ubiquitin protein ligase, which is important for spermatogenesis and motility of spermatozoa, was found to be reduced in COVID-19 patients.

In addition, the autopsied testicular specimens from COVID-19 patients were found to have several histological / physiological disorders such as erythrocyte secretion in the epididymis and testicles and spermatic thinning. In addition, the sperm tubes in COVID-19 patients were found to have higher apoptotic cells than the control.

In addition, a study performed on postmortem testicular specimens from eleven fatal cases of COVID-19 indicated several testicular histological changes such as vascular changes, basal membrane thickening, orchitis, Sertoli and Leydig cell deficiency, and reduced spermatogenesis. Color Doppler ultrasound was used to diagnose testicular abnormalities in men with mild to moderate symptoms of COVID-19. The results of the diagnosis indicated that approximately 42 percent of the men were found to have epididymitis, 19.2% had bilateralism, and 54.5 percent had enlarged epididymal head.

Impact of immune response induced SARS-CoV-2 infection on sperm quality

The immunohistochemistry of the autopsied samples obtained from COVID-19 patients showed IgG presence in seminiferous tubules and increased macrophages and T lymphocytes in the interstitial cells. In addition, higher concentrations of immune factors such as interleukin-6 and tumor necrosis factor-α were also found in semen.

SARS-CoV-2 infection was also found to increase T helper type 2 cells, disrupting the level of interleukin-4 and activating several signal transcription pathways. The disturbing level of interleukin-4 ultimately reduced ACE-2 levels with inflammation adversely affecting male fertility in COVID-19 patients.

In addition, multiorgan failure and tissue damage associated with severe cases of COVID-19 are due to the onset of cytokine storms. Another cause of tissue damage and multiorgan dysfunction may be due to hemophagocytic lymphohistiocytosis (HLH). These multiorgan damage can lead to testicular damage, which can have a negative impact on spermatogenesis and the quality of the sperm produced.

Conclusion

The present study concludes that no evidence of SARS-CoV-2 was found in semen during the symptomatic and recovery stages. However, SARS-CoV-2 infection was found to have adverse effects on sperm parameters, spermatogenesis, and sperm quality. A SARS-CoV-2 infection can also lead to testicular injury and damage and alter the expression of gonadal hormones. However, further confirmatory studies with larger populations are still desired to get the exact idea of ​​the effect of SARS-CoV-2 infection on sperm quality and spermatogenesis.

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