Neutralization of ASC improves sperm motility in men with spinal cord injury

Abstract

STUDY QUESTION: Does neutralization of apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) improve sperm motility in men with spinal cord injury (SCI)? WHAT IS KNOWN ALREADY: Semen of men with SCI contains normal sperm concentrations but abnormally low sperm motility. Inflammatory cytokines, activated via the inflammasome complex, are contributory. A key component of the inflammasome is ASC. STUDY DESIGN, SIZE, DURATION: This prospective study included semen samples collected from 32 men with SCI. PARTICIPANTS/MATERIALS, SETTING, METHODS: At a major university medical center, untreated semen was compared with semen treated with anti-ASC polyclonal antibody. Semen treated with IgG was used as a control. MAIN RESULTS AND THE ROLE OF CHANCE: Addition of anti-ASC polyclonal antibody to semen significantly increased mean sperm motility from 11.5% (95% CI, 6.3-16.7) to 18.3% (95% CI, 11.8-24.8). Improvements were most pronounced in the subgroup whose starting motility ranged between 6 and 40%. In this subgroup, the mean sperm motility improved from 13.3% (95% CI, 9.3-17.3) to 23.9% (95% CI, 14.7-23.0). Sperm motility did not improve after treatment with IgG. SUMMARY ANSWER: Neutralization of ASC improves sperm motility in men with SCI. LIMITATIONS, REASONS FOR CAUTION: This study is limited by the small sample size as this is a rare population. WIDER IMPLICATIONS OF THE FINDINGS: Blockade of the inflammasome via treatment with anti-ASC improved sperm motility in men with SCI. In doing so, this treatment significantly increased their total motile sperm count. This is the first study to demonstrate that interference with the inflammasome improves sperm motility in men with SCI. This treatment has potential as a therapeutic intervention. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Craig H. Neilsen Foundation, Grant # 224598, the University of Miami Miller School of Medicine and the Miami Project to Cure Paralysis, Miami, FL, USA. R.W.K. and J.P.d.R.V. hold a patent for the treatment of inflammation after central nervous system injury using antibodies against inflammasome proteins. The other authors have no conflicts of interest to declare.