Men with oligoasthenoteratozoospermia harbour higher numbers of multiple mitochondrial DNA deletions in their spermatozoa, but individual deletions are not indicative of overall aetiology

Abstract

It is believed that one cause of sperm dysfunction might arise through multiple mitochondrial DNA deletions (δmtDNA) resulting in the formation of an incomplete electron transport chain. This study investigates the incidence of multiple δmtDNA in human spermatozoa prepared on Percoll gradients. Firstly, we investigated for the presence of two frequently analysed δmtDNA, the 4977 and 7.4 kb deletions, using conventional polymerase chain reaction (PCR). These two deletions are characteristically flanked by direct repeats. We further analysed the incidence of one other deletion, the 15 bp deletion in the cytochrome c oxidase subunit III (COX III) of complex IV to determine whether other deletions flanked by direct repeats could be equally predictive. The incidence of these three deletions was not clearly associated with the diagnostic categorization of male infertility. However, the use of long PCR showed that samples harbouring high numbers of δmtDNA were associated with the diagnostic categorization of male infertility. We propose that these deletions could arise through a free radical-driven event occurring at the spermatogonial cell stage resulting in the replication of δmtDNA molecules at the expense of wild-type molecules. These anomalies in ejaculated sperm mtDNA could account for reproductive failure in some men.