Sperm mitochondrial DNA copy number mediates the association between seminal plasma selenium concentrations and semen quality among healthy men.

Selenium (Se) is essential for successful male reproduction. However, the association of Se status with human semen quality remains controversial and the underlying mechanisms are poorly understood. We measured seminal plasma Se concentrations, sperm mitochondrial DNA copy number (mtDNAcn), and sperm quality parameters among healthy Chinese men screened as potential sperm donors. Linear mixed-effects models were used to investigate the associations of within-subject pooled seminal plasma Se concentrations (n = 1159) with repeated sperm quality parameters (n = 5617); mediation analyses were applied to evaluate the mediating role of sperm mtDNAcn (n = 989). Seminal plasma Se concentrations were positively associated with sperm concentration and total count (both P for trend < 0.001). In adjusted models, men in the top vs. bottom quartiles of seminal plasma Se concentrations had 70.1 % (95 % CI: 53.3 %, 88.9 %) and 59.1 % (95 % CI: 40.5 %, 80.2 %) higher sperm concentration and total count, respectively. Meanwhile, we observed inverse associations between seminal plasma Se concentrations and sperm mtDNAcn, and between sperm mtDNAcn and sperm motility, concentration, and total count (all P for trend < 0.05). Mediation analyses suggested that sperm mtDNAcn mediated 19.7 % (95 % CI: 15.9 %, 25.3 %) and 23.1 % (95 % CI: 17.4 %, 33.4 %) of the associations between seminal plasma Se concentrations and sperm concentration and total count, respectively. Our findings suggest that Se is essential for male spermatogenesis, potentially by affecting sperm mtDNAcn.