Mitochondrial variations in the MT-ND4 and MT-TL1 genes are associated with male infertility

Mitochondrial gene mutations have been reported to be associated with sperm motility and the quality of semen. The aim of this study was to investigate whether the two mitochondrial genes (MT-ND4 and MT-TL1) are involved in Chinese male infertility. A total of 97 asthenospermia patients and 80 fertile controls were recruited in this case-control study. Genomic DNA were extracted from the sperm of all participants. Two mitochondrial DNA genes (MT-ND4 and MT-TL1) were amplified by using polymerase chain reaction (PCR) with the gene-specific primers and sequenced on an ABI 3730XL DNA sequencer. For the MT-ND4 gene, we found a total of 64 and 54 nucleotide substitutions in patients and controls, respectively, with no discrepancy in the mutation rates (66.0% vs. 67.5%, p>0.05). However, one mutation (g.11084A>G, p.T109A) leading to an amino acid substitution in a highly conserved residue and predicted to be deleterious was detected only in the cases. For another gene MT-TL1, a novel mutation (g.3263C>T) near the anticodon TAA was identified in an asthenospermia patient and was absent from normal controls. However, the mutation positions in the cases varied from the controls and one highly conserved mutation (g.11084A>G, p.T109A) which was not found in the controls and probably caused damage to the protein structure might contribute to asthenospermia. For another gene MT-TL1, a highly conservative novel mutation which is located closely next to the anticodon also might contribute to asthenospermia. Our result suggests that the MT-ND4 and MT-TL1 genes might be associated with Chinese male infertility.

MT-ND4: mitochondrially encoded NADH dehydrogenase 4; MT-TL1: mitochondrially encoded tRNA leucine 1 (UUA/G); PCR: polymerase chain reaction; OXPHOS: mitochondrial oxidative phosphorylation; ATP: adenosine triphosphate; mtDNA: mitochondrial DNA; SNPs: single nucleotide substitutions; AD: alzheimer's disease; PD: parkinson's disease; MELAS: mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes; ROS: reactive oxygen species.