COVID-19 and male reproductive system: pathogenic features and possible mechanisms

Abstract

Multiorgan dysfunction is the main characteristic of severe COVID-19 patients and the involvement of male reproductive system may occur among these patients. Although there is a limited evidence to confirm the orchitis and virus presence in the semen of patients, there are concerns about the transmission of virus through the semen. In addition, reduced fertility or infertility can be seen as consequences of severe COVID-19 in recovered subjects. In this study, we aimed to review articles related to COVID-19 and male reproductive system to find the possible underlying mechanisms of SARS-CoV-2 in affecting male fertility. The following keywords of SARS-CoV-2, COVID-19, testis, orchitis, semen, angiotensin-converting enzyme 2 (ACE2), hypothalamic-pituitary-testicular (HPT) axis, Hypothalamus, etc., were defined to find the related publications from standard search engines, e.g., PUBMED, SCOPUS, Google Scholar. According to studies, COVID-19 occurs in severe patients as respiratory disease, along with multi-organ failure. The most important mechanisms are classified as direct and indirect pathogenesis of SARS-CoV-2. The presence of ACE2 on the cell surface of various cells in testis increases the risk of direct infection by this virus. SARS-CoV-2 also affects the testis through the cytokine storm. In addition, the important role of HPT axis dysregulation through impaired Leydig cells and hypothalamus should be considered. Using antiviral and immunomodulatory therapy can be harmful for testis function. Further investigations are required to investigate potential mechanisms of male infertility in survivals of COVID-19. Since involvement of testis is essential for fertility, increasing the knowledge of health system may improve the outcomes.

Keywords: Angiotensin-converting enzyme 2; Coronavirus disease 2019; Cytokine storm; Hypothalamic–pituitary–testicular axis; Orchitis.

Fig. 1

Possible mechanism of SARS-COV-2 in induction of male infertility. SARS-COV-2 can affect male infertility by direct and indirect mechanisms. Directly, this virus invades cells of testicular tissue via binding ACE2 receptor. Indirectly, hyperinflammation (increased levels of cytokines), RAAS dysregulation, hypoxia, fever, brain alterations, and medical therapy can lead to dysregulation of testosterone, several pathological features, and the production of impaired sperms. IL interleukin, RAAS angiotensin–aldosterone system, ACE angiotensin-converting enzyme, TGF transforming growth factor, TNF tumor necrosis factor, IFN interferon, GE germinal epithelium, LC Leydig cells, SC Sertoli cell, OS oxidative stress, ROS reactive oxygen species (Created with BioRender.com)