Abstract
Sperm motility is one of the major determinants of male fertility. Since sperm need a great deal of energy to support their fast movement by active metabolism, they are thus extremely vulnerable to oxidative damage by the reactive oxygen species (ROS) and other free radicals generated as byproducts in the electron transport chain. The present study is aimed at understanding the impact of a mitochondrial oxidizing/reducing microenvironment in the etiopathology of male infertility. We detected the mitochondrial DNA (mtDNA) 4,977 bp deletion in human sperm. We examined the gene mutation of ATP synthase 6 (ATPase6 m.T8993G) in ATP generation, the gene polymorphisms of uncoupling protein 2 (UCP2, G-866A) in the uncoupling of oxidative phosphorylation, the role of genes such as manganese superoxide dismutase (MnSOD, C47T) and catalase (CAT, C-262T) in the scavenging system in neutralizing reactive oxygen species, and the role of human 8-oxoguanine DNA glycosylase (hOGG1, C1245G) in 8-hydroxy-2′-deoxyguanosine (8-OHdG) repair. We found that the sperm with higher motility were found to have a higher mitochondrial membrane potential and mitochondrial bioenergetics. The genotype frequencies of UCP2 G-866A, MnSOD C47T, and CAT C-262T were found to be significantly different among the fertile subjects, the infertile subjects with more than 50% motility, and the infertile subjects with less than 50% motility. A higher prevalence of the mtDNA 4,977 bp deletion was found in the subjects with impaired sperm motility and fertility. Furthermore, we found that there were significant differences between the occurrences of the mtDNA 4,977 bp deletion and MnSOD (C47T) and hOGG1 (C1245G). In conclusion, the maintenance of the mitochondrial redox microenvironment and genome integrity is an important issue in sperm motility and fertility.
Highlights
Male infertility is a growing problem that affects 30% of infertile human couples due to a decline in sperm counts and rise in testicular and sperm anomalies
We examined the gene mutation of ATP synthase 6 (ATPase6 m.T8993G) in ATP generation, the gene polymorphisms of uncoupling protein 2 (UCP2, G-866A) in the uncoupling of oxidative phosphorylation (OXPHOS), the role of genes such as manganese superoxide dismutase (MnSOD, C47T) and catalase (CAT, C-262T) in the scavenging system in neutralizing reactive oxygen species (ROS), and the role of human 8-oxoguanine DNA glycosylase in 8-OHdG repair
ATP synthesis from the mitochondrial OXPHOS system and glycolysis is essential for human sperm motility [22, 23]
Summary
Male infertility is a growing problem that affects 30% of infertile human couples due to a decline in sperm counts and rise in testicular and sperm anomalies. The evaluation of malefactor infertility has become more important and informative since new diagnostic techniques and therapeutic options have become available. Poor sperm motility has been considered as one of the major causes of male infertility [1]. It is highly probable that the respiratory dysfunction of mitochondria causes a decline in motility [2]. There remains a group of these subfertile men in whom routine semen analysis results are within normal values and who are classified as having unexplained male infertility. The presence of antisperm antibodies, sperm DNA damage, and oxidative stress has been suggested to contribute to unexplained male infertility [3]
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