Zoe Gleason, Class of 2023
SARS-CoV-2 (also known as COVID-19) has been shown to potentially have impacts upon male fertility, lowering sperm counts and concentration (Khaili et al. 2020). The cause of such effects is unknown, but it is theorized they could be due to angiotensin converting enzyme 2 (ACE-2) receptors in the male reproductive system (Illiano et al. 2020). ACE-2 is an enzyme embedded in the cell membrane that lowers blood pressure and allows some coronaviruses entrance into the cell. The male reproductive system shows a high rate of ACE-2 mRNA expression in the seminiferous duct cells, spermatogonia, Leydig cells, and Sertoli cells (Illiano et al. 2020). This shows that ACE-2 is present within the male reproductive system, therefore enabling coronaviruses to enter these cells. COVID-19 binding to ACE-2 would cause an increase in angiotensin II, as ACE-2 regulates the levels of angiotensin II. Increase in the levels of angiotensin II would cause the pulmonary symptoms seen in COVID-19 patients. However, more research needs to be conducted to determine if SARS-CoV 2 can actually access the cells in the male reproductive system.
Another theory as to how COVID-19 is affecting male fertility is that the inflammatory response interferes with the function of Leydig cells. A similar virus, SARS-CoV, showed a high number of inflammatory cells within the testicles. Since the virus is similar, it is theorized that COVID-19 could have some of the same effects as SARS-CoV and therefore could also cause inflammation in the male reproductive system (Illiano et al. 2020). Changing testosterone levels due to a loss of function of the Leydig cells could result in some of the symptoms seen in men with COVID-19. Leydig cells produce testosterone in the presence of luteinizing hormone (LH). COVID-19 patients were found to have higher levels of luteinizing hormone and prolactin (Illiano et al. 2020). Prolactin decreases testosterone levels. As these patients had maintained their testosterone levels, it is currently theorized that the levels of luteinizing hormone rose to prevent prolactin from decreasing testosterone. The rising of luteinizing hormone would only temporarily maintain testosterone levels before the increased prolactin causes the levels to drop (Illiano et al. 2020). This would cause onset of hypogonadism, the diminished function of the testes in males.
One study found that both current male patients infected with COVID-19 and patients recovered from a moderately severe infection were found to have lower sperm concentration, lower number of sperm per ejaculate, and lower motile sperm counts (Li et al. 2020). Specifically, this study diagnosed some patients with oligozoospermia, which is a low sperm count associated with infertility, and leukocytospermia. Leukocytospermia is an increase in white blood cells in the semen, which weakens sperm and can destroy genetic material, thereby leading to infertility.
Data for this study was gathered from the sperm samples of 23 men who both tested positive for COVID-19 and had offspring or proven fertility. The control group consisted of age-matched men who were also fertile. They also examined deceased patients to more fully understand the effects on the male reproductive system (Li et al. 2020). In these patients, the researchers discovered an increase in apoptotic cells in the seminal tubes, which secrete fluid like semen. The apoptotic cells are found in greater quantity due to extensive germ cell destruction from impaired spermatogenesis. They also found evidence of inflammation and the presence of ACE-2 receptors throughout the male reproductive system, both of which are theorized causes of infertility in infected males (Li et al. 2020).
More research is needed to verify these findings. The studies referenced above were limited by sample size, which can affect the accuracy of the results. These studies need to be replicated more comprehensively to be validated. Additionally, research should be conducted on the long term effects of COVID-19 on male fertility. It is important to determine if the patients’ decrease in fertility remains after they have fully recovered from the virus and, if so, how long they will remain infertile.
File:Coronavirus SARS-CoV-2.jpg - Wikimedia Commons. 2020. Commons.wikimedia.org. [accessed 2020 Dec 6]. https://commons.wikimedia.org/wiki/File:Coronavirus_SARS-CoV-2.jpg
Illiano E, Trama F, Costantini E. 2020 Jul. Could COVID-19 have an impact on male fertility? Andrologia. [accessed 2020 Dec 3]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267130/
Khalili MA, Leisegang K, Majzoub A, Finelli R, Panner Selvam MK, Henkel R, Mojgan M, Agarwal A. 2020 Oct. Male Fertility and the COVID-19 Pandemic: Systematic Review of the Literature. The world journal of men's health. [accessed 2020 Dec 3]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502312/
Li H, Xiao X, Zhang J, Zafar MI, Wu C, Long Y, Lu W, Pan F, Meng T, Zhao K, et al. 2020. Impaired spermatogenesis in COVID-19 patients. EClinicalMedicine 28:100604.