ABSTRACT
OBJECTIVE: The effects of SARS-CoV-2 were initially studied in the respiratory system, but research has now shown manifestations in multiple organ systems. SARS-CoV-2 is known to enter target cells through the ACE- 2 receptor, which is expressed in the testes. Due to this, the testes has been purported to be a potential target for SARS-CoV-2 infection. To date, studies have suggested that there is only a minor risk for shedding of SARS-CoV-2 into the semen.1 The objective of this study is to compare semen analysis parameters in a subset of healthy sperm donors prior to, during, and after testing positive for COVID-19. MATERIALSAND METHODS: The study included semen analyses (SA) from qualified sperm donors aged 19-38, with 2-5 days of abstinence who donated sperm prior to COVID infection, during active COVID infection, and post COVID infection. Semen was collected in the course of sperm bank operation and samples were collected concurrent with incidental positive test results obtained through COVID screening. Primary outcomes included ejaculate volume (mL), average concentration (M/mL), and percent motility (%). The standard operating procedure for sperm donation dictated that morphology is performed when they are first accepted into the program, thus was not recorded for these samples. Data were compared and analyzed by ANOVA. RESULTS: A total of five qualified sperm donors met inclusion criteria for this study. When comparing semen analyses across the three time points, there was not a significant difference in concentration (p=0.7460), percent motility (p=0.9135), or ejaculate volume (p=0.9241) [Table 1]. CONCLUSIONS: Sperm quality measures as evidenced in qualified, healthy sperm donors are not significantly different when comparing sperm samples prior to COVID infection, during active COVID infection, and after recovery from COVID infection. Although limited by a small sample size, our findings are reassuring to those with SARS-CoV-2 infection, as there appears to be no adverse association with sperm quality. IMPACT STATEMENT: Sperm quality in healthy, qualified donors is not affected by active SARS-CoV-2 infection.
ABSTRACT
Background: SARS-CoV-2 infection can compromise respiratory function and cause thrombotic events. SARS-CoV-2 binds to and mediates downregulation of angiotensin converting enzyme 2 (ACE2) on infected cells. Diminished enzymatic activity of ACE2 could result in increased concentrations of the pro-inflammatory molecules angiotensin II and bradykinin, contributing to SARS-CoV-2 pathology. Methods: Immunofluorescence microscopy and digital image data quantification, Computer assisted molecular docking analyses, Western blot. Results: Using immunofluorescence microscopy of lung tissues from uninfected and SARS-CoV-2 infected individuals, we find evidence that ACE2 is highly expressed in the pulmonary alveolar epithelium and is significantly reduced along the alveolar lining of SARS-CoV-2 infected lungs. Ex vivo analyses indicate that ACE2 is readily detected on primary human pulmonary alveolar epithelial and primary human aortic endothelial cells (HAoECs). Exposure of these cells to recombinant SARS-CoV-2 spike protein was sufficient to reduce surface ACE2 expression. Moreover, exposure of HAoECs to spike protein induced endothelial dysfunction (increased expression of von Willebrand Factor and decreased expression of Krüppel-like Factor 2), caspase activation, and apoptosis. Exposure of HAoECs to bradykinin (BK, 10μ M) induced calcium signaling and endothelial dysfunction but did not adversely affect viability. Computer assisted analyses of molecules with potential to bind bradykinin receptor B2 (BKRB2) suggested a potential role for aspirin as a bradykinin antagonist. When tested in our in vitro model, we found that aspirin (1μM) could significantly blunt cell signaling, and endothelial dysfunction caused by bradykinin in these cells. Conclusion: SARS-CoV-2 causes complex effects on microvascular homeostasis that potentially contribute to organ dysfunction and coagulopathies. Reduced ACE2 enzymatic activity could contribute to inflammation and pathology in the lung. Our studies add to this understanding by providing evidence that spike protein alone can mediate adverse effects on vascular cells. Understanding these mechanisms of pathogenesis may provide rationale for interventions, such as interference with the interactions of spike protein or bradykinin with endothelial cells, that could limit microvascular events associated with SARS-CoV-2 infection and stabilize microvascular homeostasis in COVID-19 disease.
ABSTRACT
OBJECTIVE: It has been suggested that geographic variations in environmental toxins may impact sperm quality. Previously, we published findings that demonstrated a decline in sperm quality over an eleven year period across six regions of the United States (US).1 The current study investigates whether there was a decrease in sperm quality from a diverse set of US sperm donors across six regions in the US over a sixteen year period. Additionally, this study sought to evaluate changes between semen analysis (SA) parameters in an era of sperm collection during the COVID-19 pandemic. MATERIALS AND METHODS: Semen analyses (SA) from sperm donors aged 19-38, with 2-5 days abstinence, from 9 different geographic regions from January 2005-April 2021 were examined. The sperm donors originated from one of the following regions: Palo Alto, Los Angeles, Westwood, International Nordic Cryo Bank Denmark, Indianapolis, Cambridge, New York, Houston, and Spokane, WA. Donation date, BMI, and geographic region were recorded. Data was analyzed as a whole as well as by individual region. Primary outcomes were ejaculate volume (mL), average concentration (M/mL), motility (%), and total motile count (M). Data was analyzed using a general estimate equation (GEE) model with an exchangeable working correlation structure to account for repeated measures. RESULTS: A total of 176,706 SA specimens (from 3,532 unique donors) were analyzed. Controlling for BMI, there was a significant decline in average concentration (M/mL) (β=-1.89, p<0.0001), sperm motility (%) (β=-0.2892, p<0.0001) and total motile sperm (M) (β=-4.53, p<0.0001) over the 16-year study period. There were significant decreases in SA parameters within all geographic regions (Spokane only had two unique donors and could not be examined). Indianapolis showed a significant decrease in sperm concentration and total motile sperm, but also displayed an increase in sperm motility over the study period. CONCLUSIONS: Time related decline in sperm quality continues to be evident at a national level in young, healthy sperm donors. There was a decline across all geographic regions in all parameters except for ejaculate volume. How this decline in sperm counts impacts fertility has yet to be determined. Our modern environment involves increased exposures to endocrine disruptors and changes to lifestyle (including smoking, diet, and stress) that are postulated to impair male fertility by interfering with spermatogenesis. While a causative link to these risk factors remains to be elucidated further studies are necessary to evaluate whether this temporal decline in sperm count correlates with decreased fecundity. IMPACT STATEMENT: Sperm concentration, motility, and total motile sperm continue to decline across young, healthy sperm donors across the continental United States.