Potential mechanisms of SARS‐CoV‐2 action on male gonadal function and fertility: Current status and future prospects

Abstract

The novel coronavirus was recognised in December 2019 and caught humanity off guard. The virus employs the angiotensin‐converting enzyme 2 (ACE2) receptor for entry into human cells. ACE2 is expressed on different organs, which is raising concern as to whether these organs can be infected by the virus or not. The testis appears to be an organ enriched with levels of ACE2, while the possible mechanisms of involvement of the male reproductive system by SARS‐CoV‐2 are not fully elucidated. The major focus of the present studies is on the short‐term complications of the coronavirus and gains importance on studying the long‐term effects, including the possible effects of the virus on the male reproductive system. The aim of this review was to provide new insights into different possible mechanisms of involvement of male gonads with SARS‐CoV‐2 including investigating the ACE2 axis in testis, hormonal alterations in patients with COVID‐19, possible formation of anti‐sperm antibodies (ASA) and subsequently immunological infertility as a complication of SARS‐CoV‐2 infection. Finally, we suggest measuring the sperm DNA fragmentation index (DFI) as a determiner of male fertility impairment in patients with COVID‐19 along with other options such as sex‐related hormones and semen analysis. Invasion of SARS‐CoV‐2 to the spermatogonia, Leydig cells and Sertoli cells can lead to sex hormonal alteration and impaired gonadal function. Once infected, changes in ACE2 signalling pathways followed by oxidative stress and inflammation could cause spermatogenesis failure, abnormal sperm motility, DNA fragmentation and male infertility.