COVID-19 potentially has negative impacts on male fertility

A review recently posted on Journal of Medical Virology discussed some of the effects infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent that causes coronavirus disease 2019 (COVID-19), can have on male fertility.

In the paper, Cemile Seymen of the Gazi University Institute of Health Sciences, in Ankara, Turkey, summarizes the study results that show how the infection can adversely affect male reproductive health.

Seymen says more studies are needed to investigate the roles that host cell proteins of the angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) may play in infection since both of these proteins, which are involved in viral entry, are highly expressed in the male reproductive system.

Very little data is available on the effects of COVID-19 on male fertility

Since SARS-CoV-2 was first identified in Wuhan, China late last year (2019), studies have shown that the virus not only causes respiratory disease, but can affect various different organs. including those of the male reproductive system.

“There is a very limited amount of data on the effects of COVID-19 on male fertility, so it has become an important topic for researchers,” Seymen says.

ACE2 is highly expressed in the male genital tract

To achieve viral entry, SARS-CoV-2 uses a surface structure called a spike protein to bind to the ACE2 receptor found on host cells.

A study published earlier this year showed that ACE2 messenger RNA was expressed in both germline and somatic cells of the testis. Other studies have found that ACE2 is expressed in spermatogonia, Leydig cells and Sertoli cells.

A study that used electron microscopy to examine postmortem tissue from the testes of twelve COVID-19 patients demonstrated swelling, vacuolation, and cytoplasmic dilution in Sertoli cells and a reduction in Leydig cell numbers, compared to patients who did not they had COVID-19.

Some studies have also shown increased levels of the SQSTM1 autophagy receptor in cells infected with SARS-CoV-2, indicating a decrease in autophagic flux.

“As a result, SARS-CoV-2 can cause male reproductive disorders by regulating the level of autophagy in male germ cells,” writes Seymen.

The researchers also proposed that an increase in testicular temperature as an indirect effect of inflammation negatively impact the testes among COVID-19 patients.

What about TMPRSS2?

Seymen also discusses the role that TMPRSS2 may play in SARS-CoV-2 infection of the prostate.

One study found that this enzyme, which cleaves the spike protein in preparation for virus and host membrane fusion, is highly expressed in the prostate epithelium.

This gland secretes prostate fluid, one of the main components of seminal fluid. The muscles within the gland are responsible for pushing semen through the urethra during ejaculation.

High expression of TMPRSS2 within the prostate could increase the likelihood of SARS-CoV-2 infection in this gland, which could affect its ability to secrete these fluids, Seymen says.

Effects on the nervous system could affect male fertility

Seymen points out that SARS-CoV-2 could also indirectly exert negative impacts on male fertility, through mechanisms involving the nervous system.

For example, most viruses permeate the blood-brain barrier, and reports have shown that glial cells and neurons also express ACE2 receptors, potentially making them a target for SARS-CoV-2-induced neuronal death.

Importantly, the central nervous system plays a vital role in endocrine control and spermatogenesis. Neurons in the hypothalamus secrete gonadotropin-releasing hormone (GnRH), for example, which triggers the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland.

Low levels of GnRH result in a decrease in FSH and LH, which in turn affects the function of Sertoli cells and Leydig cells.

Seymen also points out that depression and anxiety (which many people are experiencing during the current pandemic) are associated with increased cortisol and prolactin levels, as well as lower sperm count and sperm volume, which all have. proven to contribute to dysfunction.

Further studies are needed

Seymen says that taken together, these study results suggest that the COVID-19 pandemic affects the male reproductive system in both direct and indirect ways.

“Further studies are needed to answer all questions and further investigation is warranted, but ACE2 and TMPRSS2 play an important role in the cellular entry of SARS-CoV-2. As the male genital system exhibits high expression of ACE 2, the importance of this path increases in cases of COVID-19, “he concludes.