Lipid peroxidation and large-scale deletions of mitochondrial DNA in asthenoteratozoospermic patients

The correlation between malondialdehyde (MDA) an index of lipid peroxidation (LPO) with large-scale deletion mitochondrial DNA (mtDNA) was investigated in a case-control study with a total of 50 semen samples from infertile men, including 25 normozoospermic donor as the control group and 25 asthenoteratozoospermic (AT) patients as the case group. Routine semen analysis was performed according to World Health Organization (WHO, 1999) guidelines. MDA levels of the seminal plasma and spermatozoa were measured by TBARS method. A long-range polymerase chain reaction (PCR) method was used for the analysis of multiple large-scale mtDNA deletions based in two areas of mtDNA. The results showed that mean concentration of MDA in seminal plasma (nmol/ml) and spermatozoa (nmol/10 x 10(6) sperm) of AT men was higher than in normozoospermic patients, but the differences were not statistically significant. The products of PCR analysis showed multiple deletions of approximately 4.7, 4.8, 7.2, 7.3 and 7.4-kb in mtDNA of the spermatozoa in both AT and control groups. Multiple deletions were also observed in 64% of AT patients and 44% of the control group. Moreover, MDA level of the spermatozoa in deleted mtDNA samples group was significantly higher than in non-deleted mtDNA group (p = 0.01). Our findings indicated a positive correlation between increased MDA levels and large-scale mtDNA deletions in human spermatozoa. It is suggested that LPO or other oxidative stress factors might be causative elements in mtDNA damage, effect on sperm motility and morphology, resulting in decline of fertility in men.