MITOCHONDRIAL DEOXYRIBONUCLEIC-ACID 4977-BP DELETION IS ASSOCIATED WITH DIMINISHED FERTILITY AND MOTILITY OF HUMAN SPERM

The accumulation of mitochondrial DNA (mtDNA) mutations has been sugge sted to be an important contributor to human aging and degenerative di seases. In previous studies, we found an age-dependent increase of mtD NA mutations in various human tissues. Sperm motility is one of the de terminants of male fertility. The possible relationship between mtDNA deletions and diminished fertility and motility of sperm was explored in the present study. We examined accumulation of the 4977-bp mtDNA de letion in spermatozoa obtained from patients with infertility or subfe rtility and compared these values with those of normal individuals. Us ing polymerase chain reaction (PCR) techniques, we determined the freq uency of occurrence and the proportion of mtDNA with the 4977-bp delet ion in human spermatozoa with different motilities. Human spermatozoa were separated by self-migration in Percoll gradients into five fracti ons with different motility scores. The highest frequency of occurrenc e of the 4977-bp mtDNA deletion was found in sperm in the fraction wit h the lowest motility. The results revealed a negative correlation bet ween sperm motility and the proportion of 4977-bp-deleted mtDNA. Furth ermore, we found a significantly higher incidence of the 4977-bp mtDNA mutation in patients with asthenospermia, oligospermia, and primary i nfertility compared to normal individuals. These findings suggest that mtDNA mutations may play an important role in some pathophysiological conditions in human spermatozoa.