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A review recently published in Journal of Medical Virology has analyzed some of the effects that infection with coronavirus 2 (SARS-CoV-2), severe acute respiratory syndrome, can have on male fertility.
In the article, Cemile Seymen from the Institute of Health Sciences at Gazi University, Ankara, Turkey, summarizes the study findings showing how the infection can negatively affect male reproductive health.
Seymen says more studies are needed to investigate the roles that host cell proteins, angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) can play in infection, as both proteins, which are involved At viral entry, they 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 illnesses, but can affect several different organs, including the 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 highly expressed in the male genital tract
To gain 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 testes. Other studies have found that ACE2 is expressed in spermatogonia, Leydig cells, and Sertoli cells.
A study using electron microscopy to examine post-mortem tissues from the testes of twelve COVID-19 patients demonstrated swelling, vacuolation, and cytoplasmic dilution in Sertoli cells and a reduction in the number of Leydig cells, compared to patients who they did not have COVID-19.
Some studies have also shown increased levels of the autophagy receptor SQSTM1 in cells infected with SARS-CoV-2, indicating a drop in autophagy flux.
“As a result, SARS-CoV-2 can cause male reproductive disorders by regulating the level of autophagy in male germ cells,” Seymen writes.
Researchers have also proposed that an increase in testicular temperature as an indirect effect of inflammation has negative impacts on the testicles 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 tip protein in preparation for fusion of the virus and the host membrane, is highly expressed in the epithelium of the prostate.
This gland secretes prostate fluid, one of the main components of seminal fluid. The muscles within the gland are responsible for pushing seminal fluid 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 can affect its ability to secrete these fluids, Seymen says.
Effects on the nervous system may affect male fertility
Seymen points out that SARS-CoV-2 could also have negative impacts on male fertility indirectly, through mechanisms that involve 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 fundamental 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 GnRH levels result in a decrease in FSH and LH, which in turn affects the function of Sertoli cells and Leydig cells.
Seymen also notes that depression and anxiety (which many people are experiencing during the current pandemic) are associated with increased levels of cortisol and prolactin, as well as a lower sperm count and semen volume, all of which have been shown. that contributes to sexual activity. dysfunction.
More studies are needed
Taken together, Seymen says, these study findings suggest that the COVID-19 pandemic affects the male reproductive system in direct and indirect ways.
“Additional studies are needed to answer all the questions and more research is warranted, but ACE2 and TMPRSS2 play an important role in the cellular entry of SARS-CoV-2. Because the male genital system exhibits high expression of ACE 2 , the importance of this pathway increases in cases of COVID-19 “, he concludes.
