Low dose of cyclosporine A disrupts sperm parameters and testosterone levels reversibly in mice

Abstract

The prevalence of autoimmune diseases has increased worldwide, including in men of reproductive age. Cyclosporine A (CsA) is an immunosuppressive drug commonly used for long periods in the prophylaxis and treatment of autoimmune dysfunction and transplant rejection. Owing to CsA toxicity, most clinical settings use lower CsA doses. Therefore, we evaluated whether a low dose (10 mg/kg) of CsA affects sperm parameters (daily sperm production, motility, morphology, mitochondrial activity, and acrosomal integrity), plasma testosterone levels, and fertility after short-term (10 days) and long-term (50 days) treatments in mice. Short-term CsA treatment partially affected sperm parameters and fertility, as shown by the reduction in sperm hyperactivation and gestational rate 10 days after the interruption of short-term CsA treatment. Long-term CsA treatment impairs sperm count, hyperactivated motility, and acrosomal integrity. This treatment regimen further decreased plasma testosterone concentrations but did not affect reproductive outcomes in mating trials. These outcomes were reversed 50 days after the interruption of long-term CsA treatment. We conclude that a low CsA dose differentially impairs sperm parameters and testicular steroidogenesis in a time-dependent and mostly reversible manner but does not affect male fertility.

Keywords: Calcineurin Inhibitor; Immunosuppressants; Mouse; Reproductive Toxicity; Sperm Motility; Spermatozoa.