High incidence of single nucleotide substitutions in the mitochondrial genome is associated with poor semen parameters in men

Single nucleotide polymorphisms (SNPs) in 7000 bp of the mitochondrial geno me, encompassing 15 coding regions from COI to ND5, were characterized by s ingle strand polymorphism analysis and confirmed by DNA sequencing. About 2 .4% of normo-zoospermic men and 8.4% of men with poor semen quality had at least one nucleotide substitution. Most of the substitutions occurred in th e third codon and did not change the amino acid. Hydrophobicity plots of th e proteins with changes in an amino acid as a result of a nucleotide substi tution suggested that they did not affect the function of the protein. The two most common substitutions at nucleotide (nt) 9055 and 11719 had signifi cantly higher frequencies in men with reduced sperm motility. Eleven percen t of the men with poor semen parameters and 1.3% of normozoospermic men had a 9055 substitution, 12% of the men with poor semen parameters had a subst itution at nt 11719, but none of the normozoospermic men had this substitut ion. All the patients with these substitutions had reduced sperm, motility and/or low sperm count. These SNPs in the mitochondrial genome were in a ho moplasmic state. Thus, we propose that possessing these mitochondrial mutat ions compromises the semen quality of these men.