Impact of SARS-CoV-2 infection on testicular function
Several studies have been done around the world on the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the lungs and the immune system, but little is known about the virus’s effects on male fertility. Entry of SARS-CoV-2 is mediated by the presence of angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2) and furin. Therefore, host cells expressing these proteins are very sensitive to viral entry.
There is currently no clear report on the expression of these entry proteins in the testes.
A study published in the journal Nature Urology Reviews discusses the impact of coronavirus disease 2019 (COVID-19) on male fertility. The authors of this article used the available data on the mechanism of SARS-CoV-2 infection, risk factors, symptoms, organs affected, long-term and short-term effects, and others to understand the effect. of COVID-19 on testicular function.
Expression of furin, ACE2 and TMPRSS2
Although the primary target of SARS-CoV-2 is the respiratory organs, including the upper respiratory tract and lungs, many symptoms affect multiple organs such as the blood and heart vessels, liver, brain, and male genitals. have also been reported. This indicates that SARS-CoV-2 accesses several organs which express viral input proteins and damage them directly or indirectly.
The SARS-CoV-2 spike glycoprotein mediates virus entry into host cells and determines viral infectivity, immune response, host range, and tissue tropism. Some studies have shown that the ACE2 receptor is expressed in myoid, Leydig and Sertoli cells and in spermatogonia, indicating a high sensitivity of these cells to SARS-CoV-2. Expression of TMPRSS2 has been demonstrated in spermatogonal stem cells (SSC), spermatocytes, spermatogonia and spermatids. Many secondary sex organs like the prostate, adrenal glands, and seminal vesicles express both ACE2 and TMPRSS2.
ACE2 plays an essential role in the regulation of the renin-angiotensin-aldosterone system (RAAS) which is overactivated due to COVID-19 comorbidities such as hypertension and diabetes. Overactivation of RASS results in upregulation of ACE2, thereby increasing entry points for SARS-CoV-2. Some studies have shown that RAAS is activated more in men than in women, indicating higher levels of ACE2 in men, which may explain the serious consequences of COVID-19 in men than in women. .
Studies show that SARS-CoV-2 can alter hormone production by inhibiting ACE2, which can interfere with the hypothalamic-pituitary-gonadal (HPG) axis and alter the level of follicle stimulating hormone (FSH) ), luteinizing hormone (LH), and testosterone and can potentially lead to impaired spermatogenesis, hypogonadism and infertility.
Clinical studies in patients with COVID-19
SARS-CoV-2 has a similar pathology to SARS-CoV, which is known to cause testicular dysfunction or inflammation (orchitis). Numerous studies have reported cases of testicular pain, orchitis, epididymitis or epididymo-orchitis, and altered hormonal levels in COVID-19 patients. The presence of SARS-CoV-2 in semen is still not confirmed, but some studies have detected viral RNA in semen, which could suggest the transmission of the virus through sex and its direct effect on semen. Although the presence of the virus in semen is of concern, it does not necessarily have a negative effect on fertility. Despite this, semen testing is crucial in future studies to rule out the presence of SARS-CoV-2.
Currently available information on the effect of SARS-CoV-2 infection on reproductive organs and reports of symptoms such as testicular pain, orchitis and hormonal changes raise concerns about a possible negative impact of SARS-CoV-2 on testicular function. It remains to be seen whether these symptoms stem from the direct effects of SARS-CoV-2 on the testes or are mediated by other mechanisms, such as the immune response and inflammation.
According to the authors, a systematic approach is needed to identify the possible effects of SARS-CoV-2 on male fertility. The first step in this approach should be to determine the viral presence in the testes or semen in human cohorts divided mainly on the basis of their age and disease state. Studies on in vitro and in vivo animal models could help determine the presence of the virus in semen or testes and its effects on male fertility.
Edenfield RC and Easely CA 2021. Implications of testicular ACE2 and the renin-angiotensin system for SARS-CoV-2 on testicular function. Nature Urology Reviews. do I: https://doi.org/10.1038/s41585-021-00542-5 https://www.nature.com/articles/s41585-021-00542-5