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

It is believed that one;cause of sperm dysfunction might arise through mult iple mitochondrial DNA deletions (Delta mtDNA) resulting in the formation o f ap incomplete electron transport chain. This study investigates the incid ence of multiple Delta mtDNA in human spermatozoa prepared on Percoll gradi ents. Firstly, we investigated for the presence of two frequently analysed Delta mtDNA, 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, t he 15 bp deletion in the cytochrome c oxidase subunit III (COX III) of comp lex IV to determine whether other deletions flanked by direct repeats could be equally predictive. The incidence of these three deletions was not clea rly associated with the diagnostic categorization of male infertility. Howe ver, the use of long PCR showed that samples harbouring high numbers of Del ta mtDNA were associated with the diagnostic categorization of male inferti lity. We propose that these deletions could arise through a free radical-dr iven event occurring at the spermatogonial cell stage resulting in the repl ication of Delta mtDNA molecules at the expense of wild-type molecules. The se anomalies in ejaculated sperm mtDNA could account for reproductive failu re in some men.