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Abstract
The existing evidence suggests that the human reproductive system may be potentially vulnerable to COVID-19 infection. However, little is known about the virus–host interaction of COVID-19 in sperm cells. We are the first to address the connection between changes in multiple seminal biomarkers and reproductive function in male patients recovering from COVID-19. In a prospective longitudinal cohort study, seminal ACE2 activity, markers of inflammation and oxidative stress, apoptotic variables, and semen quality parameters were evaluated at 10-day intervals for a maximum follow-up time of 60 days among male patients with laboratory-confirmed COVID-19 (n = 84) and healthy controls (CON; n = 105). At the baseline and the subsequent follow-ups, the COVID-19 group revealed significantly higher levels of seminal plasma ACE2 enzymatic activity, IL-1β, IL-6, IL-8, IL-10, TGF-β, TNF-α, IFN-α, IFN-γ, ROS, caspase-8, caspase-9, and caspase-3 activity as well as lower levels of SOD activity than those in the CON group (P < 0.05). These perturbations tended to persist over time and were correlated with significant impairments in semen volume, progressive motility, sperm morphology, sperm concentration, and the number of spermatozoa. We provide the direct experimental evidence that the male reproductive system could be targeted and damaged by the COVID-19 infection. These findings go beyond our current understanding of the disease, suggesting that the reproductive function of the patients recovering from the disease should be precisely followed and evaluated to detect and avoid more serious reproductive problems in the future, as they may develop a transient state of male subfertility like those with oligoasthenoteratozoospermia.
Introduction
Since the first report in Wuhan, Hubei Province of China, in late December 2019, the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has spread worldwide exponentially, leading to the coronavirus disease (COVID-19) being confirmed a global pandemic outbreak by the World Health Organization (WHO) on the March 11, 2020. As of December 25, 2020, over 79 million cases of COVID-19 have been confirmed, and approximately 1,740,423 official deaths have been declared globally. The virus that causes COVID-19 leads to acute respiratory distress syndrome with severe respiratory symptoms and relatively high fatality risk (Chan et al. 2020, Chen et al. 2020, Huang et al. 2020). It is predominantly transmitted via close contact with an infected patient and with infected large respiratory droplets propagated when an infected person speaks, exhales, sneezes, or coughs (Chan et al. 2020, Liu et al. 2020b). Recent structural and functional evidence reported that due to having a strong binding affinity to the human cell receptor, angiotensin-converting enzyme 2 (ACE2), COVID-19 employs this receptor, in synergy with the host’s type II transmembrane serine protease (TMPRSS2) (Mollica et al. 2020), for entry into target host cells (Hoffmann et al. 2020, Zhao et al. 2020). Accordingly, the cells expressing these receptors may function as the target cells and consequently might let COVID-19 entry, proliferation, propagation, and pathogenesis (Chai et al. 2020, Mollica et al. 2020, Zhang et al. 2020, Zhou et al. 2020, Zou et al. 2020). It has been declared that ACE2 and TMPRSS2 are highly expressed not only in the lungs, kidney, intestine, and heart tissues (Gkogkou et al. 2020, Zhou et al. 2020) but in the spermatogonia, Leydig, and Sertoli cells in the human testes (Fan et al. 2020), as well as in other male reproductive organs like the prostate gland (Maya & Carvajal 2020), the seminal vesicles, and the bulbourethral glands (Zupin et al. 2020), that contribute seminal fluid to the semen, suggesting that COVID-19 could infect the male reproductive organs and risk male reproduction (Fan et al. 2020). In this regard, the impaired spermatogenesis (Li et al. 2020) and declined sperm quality parameters (Ruan et al. 2020) have already been detected in COVID-19 patients. However, the association and the infection-induced-longitudinal changes in the male reproductive function in COVID-19 patients are not clear. Also, the exact mechanisms behind these observations remain an under-researched issue.
To address this query, therefore, we examined the temporal changes in seminal ACE2 enzymatic activity, pro- and anti-inflammatory cytokines, oxidative and antioxidative parameters, apoptotic variables, and semen quality parameters in reproductive-aged Iranian male patients recovering from COVID-19 and age-matched healthy controls, measured at 10-day intervals for a maximum follow-up time of 60 days, and defined their associations with male reproductive function.
source https://rep.bioscientifica.com/view/journals/rep/161/3/REP-20-0382.xml
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