Dysregulation of mitochondrial sirtuin genes is associated with human male infertility.

Mitochondrial sirtuins (SIRT3, SIRT4, SIRT5) are post-translational modifiers that regulate energy production, body homeostasis and mitochondrial activities via different substrates in response to environmental stressors. The present study aimed at assessing the expression of SIRT3, SIRT4, and SIRT5 in the semen of infertile men. Expression analysis was performed using q-RT PCR. All mitochondrial sirtuin genes were significantly down-regulated in the semen of infertile men compared to fertile men. Mitochondrial sirtuin genes expression levels were correlated with mitochondrial HSP90 expression. HSP90 expression was positively correlated with SIRT3, SIRT4 and SIRT5 expression in the semen of fertile men, while a negative correlation was observed between HSP90 in the semen of infertile men and mitochondrial sirtuin genes in the semen of fertile men. These data suggest that dysregulation of mitochondrial sirtuin genes causes mitochondrial dysfunction due to stress, which appears to be associated with human male infertility by compromising functional and structural sperm integrity.