How will COVID-19 and its treatment affect testicular function?

More than 627 million people worldwide are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing coronavirus disease 2019 (COVID-19).

study: COVID-19 and its treatment: Lights and shadows of testicular function. Image credit: Chinnapong / Shutterstock.com

Background

Compared to women, men are more susceptible to COVID-19 and its effects. This is due to multiple factors, including genetic background, sex-specific hormones, and lifestyle patterns.

As a result, researchers have investigated whether SARS-CoV-2 is present in semen and affects testicular function. Reproductive health in men has been assessed after SARS-CoV-2 infection based on reproductive his outcomes, changes in semen parameters, and other aspects.

The long-term effects of COVID-19 on male reproductive health are also being studied, as changes in the hormonal axis and gametic disorders have been reported. These studies demonstrate that both SARS-CoV-2 infection and its treatment can affect male reproductive health.

recently endocrine Researchers have compiled the available information about the reproductive effects of COVID-19. This can be very useful for endocrinologists to develop preventative measures. For this mini-review, the author obtained all relevant articles from her Medline/PubMed and Embase.

How does COVID-19 affect testicular function?

SARS-CoV-2 infects the host by binding to the host cell’s angiotensin-converting enzyme 2 (ACE2) receptor. Membrane fusion then occurs to establish the infection. Interestingly, ACE2 was found to be expressed in male germ cells such as spermatogonia, Leydig cells, Sertoli cells and seminiferous tubule cells.

Besides ACE2, several mediators, such as the transmembrane protease Serine 2, are required to facilitate virus-host cell fusion (TMPRSS2). TMPRSS2 is expressed in human prostate epithelial cells and androgens regulate its expression in the male reproductive system.

A theoretical possibility of COVID-related testicular damage is supported by post-mortem detection of viral proteins in testicular tissue. To infect testis cells, the virus must overcome the blood-testis barrier. This can be achieved through cytokine-induced inflammation that alters Sertoli cell tight junctions.

A recent meta-analysis reported the presence of small amounts of SARS-CoV-2 in semen samples from infected individuals. Nevertheless, few studies have reported an association between SARS-CoV-2 infection and testicular discomfort and pain. A histological study detected orchitis, possibly due to vasculitis, in a patient who died from severe COVID-19-associated multiple organ failure.

Based on previous studies, SARS-CoV-2-associated testicular endothelial dysfunction may induce the synthesis of CD3+ and CD68+ leukocytes, as well as other inflammatory cells in interstitial tissue. However, in most COVID-19 cases, no direct damage to seminiferous tubules and spermatogenesis was observed, especially in the absence of comorbidities.

Indirect damage to testicles

Various indirect mechanisms such as fever, inflammation, and gonatotoxic treatments can damage the testis.

Testicular temperature may be altered by fever, which may adversely affect germ cell development. In addition, the condition may also adversely affect semen quality and sperm DNA integrity.

Thus, COVID-19 fever could stimulate changes in sperm parameters even in the absence of SARS-CoV-2 in semen. However, one meta-analysis reported that COVID-19 fever- or treatment-induced impairment of sperm production was corrected after the patient recovered.

SARS-CoV-2 infection can significantly alter the levels of several pro-inflammatory mediators that induce testicular damage. For example, cytokines cause inflammation of the male reproductive organs and are important factors that increase the risk of infertility.

In addition, proinflammatory cytokines can alter the microenvironment of the seminiferous tubules, which may be related to changes in Sertoli cell tight junctions, thereby affecting blood-testis barrier permeability. give. Cytokines also cause oxidative stress and induce germ cell apoptosis.

Dysregulated cytokines and chemokines can stimulate autoimmune responses, affect testicular tissue and semen quality, and reduce the fertilizing capacity of sperm and gamete fusion. SARS-CoV-2 infection also impairs gonadal hormone function at low testosterone levels.

Effects of COVID-19 drugs and vaccines on testicular function

Many drugs have been found to interfere with spermatogenesis. Hydroxychloroquine was one of the drugs originally used to treat COVID-19. However, animal studies revealed that the drug decreased sperm count, testicular weight, accessory genitalia, and testosterone secretion.

Several antiviral drugs such as darunavir/ritonavir, lopinavir/ritonavir, nilmatrelvir-ritonavir, molpunavir and remdesivir are being used for COVID-19 treatment.Antiviral drugs have been associated with causing changes in semen parameters, but high-quality evidence supporting this effect is not yet available.in vivo Animal studies have shown that some antiviral drugs, such as lopinavir/ritonavir, adversely affect sperm parameters, possibly through increased oxidative stress.

Importantly, COVID-19 messenger ribonucleic acid (mRNA)-based vaccines showed no adverse effects on semen volume and motility of sperm concentration.To determine sperm morphology after COVID-19 vaccination , which requires further research.