Involvement of the inflammasome in abnormal semen quality of men with spinal cord injury

Capsule:
This study provides the first evidence that inflammasome proteins are present in human 24 semen, and suggests that the inflammatory innate immune response contributes to 25 abnormal semen quality in SCI men.

Authors:
Xianyang Zhang, Ph.D., Emad Ibrahim, M.D., Juan Pablo de Rivero Vaccari, Ph.D., George Lotocki, Ph.D., Teodoro C. Aballa, M.S., W. Dalton Dietrich, Ph.D., Robert W. Keane, Ph.D., Charles M. Lynne, M.D., Nancy L. Brackett, Ph.D., H.C.L.D.

Volume 99, Issue 1, Pages 118-124.e2, January 2013

Abstract:
Objective:
To study the mechanism leading to elevated semen cytokines in men with SCI and to understand if inflammasome pathways are involved in this process. This study investigated inflammasome components and end-product cytokines in semen of SCI and control subjects.

Design:
Prospective study.

Setting:
Major university medical center.

Patient(s):
Men with and without SCI (n=28 per group).

Interventions:
None.

Main Outcome Measure(s):
Seminal plasma concentrations of caspase-1, IL-1β and IL-18 were quantified by ELISA. Caspase-1 in sperm fractions and apoptosis-associated speck-like protein containing a CARD [Caspase Activation and Recruitment Domain] (ASC) in seminal plasma and sperm fractions were identified by Western blot. Localization of proteins in sperm was accomplished by immunocytochemistry.

Results:
ASC, caspase-1, IL-1β and IL-18 concentrations were elevated in the seminal plasma of SCI subjects compared to control subjects. ASC and caspase-1 were elevated in sperm cells of SCI subjects. Immunocytochemistry revealed that ASC was located in the acrosome, equatorial segment and midpiece, and caspase-1 in the midpiece.

Conclusions:
This study provides the first evidence of ASC in human semen and demonstrates the involvement of inflammasome proteins in semen of men with SCI. These findings suggest an immunologic basis for abnormal semen quality in men with SCI.

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