A review recently published in the Journal of Medical Virology has discussed some of the effects that coronavirus 2 (SARS-CoV-2) infection – the causative agent of coronavirus disease 2019 (COVID-19) – can have on men’s fertility.
In the article, Cemile Seymen from the Institute of Health Sciences at Gazi University in Ankara, Turkey summarizes study results that show how the infection can negatively impact men’s reproductive health.
According to Seymen, more studies are needed to investigate the role that angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) of host cell proteins can play in infections, as both proteins are involved in virus entry , play a high role 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 diseases, but can affect various 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,” says Seymen.
ACE2 is strongly 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 present on host cells.
A study published earlier this year showed that ACE2 messenger RNA was expressed in both germ and somatic cells of the testicle. Other studies have shown that ACE2 is expressed in spermatogonia, Leydig cells, and Sertoli cells.
A study that used electron microscopy to examine post-mortem tissues from the testes of twelve COVID-19 patients showed swelling, vacuolization and cytoplasmic thinning in the Sertoli cells and a reduction in the number of Leydig cells compared to patients without COVID-19.
Some studies have also shown increased levels of the autophagy receptor SQSTM1 in cells infected with SARS-CoV-2, indicating a decrease in autophagy flux.
“As a result, SARS-CoV-2 can cause male reproductive disorders by regulating the extent of autophagy in male germ cells,” writes Seymen.
Researchers have also suggested that an increase in testicular temperature, as an indirect effect of inflammation, has negative effects on the testes in COVID-19 patients.
What about TMPRSS2?
Seymen also discusses the role that TMPRSS2 can 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. Muscles in the gland are responsible for pushing semen through the urethra during ejaculation.
The high expression of TMPRSS2 in the prostate could increase the likelihood of SARS-CoV-2 infection in that gland, which could affect the ability to secrete these fluids, says Seymen.
Effects on the nervous system can affect male fertility
Seymen points out that SARS-CoV-2 could also have negative effects on male fertility indirectly through mechanisms that affect the nervous system.
For example, most viruses cross 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 critical role in endocrine control and spermatogenesis. For example, neurons in the hypothalamus secrete gonadotropin-releasing hormone (GnRH), which triggers the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland.
Low GnRH levels lead to 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 linked to increased cortisol and prolactin levels, as well as lower sperm counts and semen volume, all of which have been shown to contribute to sex and dysfunction .
More studies are needed
Seymen says that when taken together, these study results suggest that the COVID-19 pandemic affects the male reproductive system both directly and indirectly.
“Additional studies are needed to answer any questions and more research is needed, but ACE2 and TMPRSS2 play an important role in the cellular onset of SARS-CoV-2. Since the male genital system is high in ACE 2 expression, this is it important In COVID-19 cases, the signal path increases, “she concludes.