Mitochondrial DNA mutations in etiopathogenesis of male infertility (original) (raw)
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ZOOLOGICAL STUDIES-TAIPEI-, 2000
Yau-Huei Wei and Shu-Huei Kao (2000) Mitochondrial DNA mutation and depletion are associated with decline of fertility and motility of human sperm. Zoological Studies 39(1): 1-12. Sperm motility is one of the most important determinants of male fertility. In this review, we discuss recent findings that mutation and depletion of mitochondrial DNA (mtDNA) are associated with poor motility and diminished
Genetic Association in the Maintenance of the Mitochondrial Microenvironment and Sperm Capacity
Oxidative Medicine and Cellular Longevity, 2021
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-hydr...
Role of Human Sperm Mitochondrial DNA in Infertility
2015
Sperm is the core of male fertility, which has to travel up to the fallopian tube for successful fertilization. Sperm motility depends on the electron transport chain producing ATPs in its mitochondria, which is a direct expression of the mitochondrial DNA (mtDNA) quality. Sperm motility is major determinant of fertility. It is already believed that mtDNA mutations are linked with infertility but the results are contradictory and previous researches are based on limited number of semen samples. Previous studies indicated a vacuum for more comprehensive study of sperm mtDNA from multiple aspects with sufficient number of carefully selected subjects to find more concrete findings. This case control study was designed on these hard facts to find association of sperm mtDNA deletions with fertility. We hypothesized that sperm mtDNA deletions have significantly associations with human male infertility. We collected 355 human semen samples (following WHO protocols), 74 samples normal contr...
Sperm mitochondrial mutations as a cause of low sperm motility
Journal of andrology
We report the unique case of a 28-year-old man who, in spite of having a varicocele and a sperm concentration of 5 million/mL, of which 10% were motile and 20% had normal forms (oligoasthenoteratozoospermia [OAT]), was fertile. This was confirmed by paternity testing using 16 autosomal and 6 Y-chromosomal short tandem repeat (STR) loci. An analysis of mitochondrial genes that included cytochrome oxidase I (COI), cytochrome oxidase II (COII), adenosine triphosphate synthase6 (ATPase6), ATPase8, transfer ribonucleic acid (tRNA) serine I, tRNA lysine, and NADH dehydrogenase3 (ND3) revealed, for the first time, 9 missense and 27 silent mutations in the sperm's mitochondrial DNA (mtDNA) but not in the DNA from the blood cells. There was a 2-nucleotide deletion in the mitochondrial COII genes, introducing a stop codon, which might be responsible for low sperm motility.
Biology of Reproduction, 1995
The accumulation of mitochondrial DNA (mtDNA) mutations has been suggested to be an important contributor to human aging and degenerative diseases. In previous studies, we found an age-dependent increase of mtDNA mutations in various human tissues. Sperm motility is one of the determinants of male fertility. The possible relationship between mtDNA deletions and diminished fertility and motility of sperm was explored in the present study. We examined accumulation of the 4977-bp mtDNA deletion in spermatozoa obtained from patients with infertility or subfertility and compared these values with those of normal individuals. Using polymerase chain reaction (PCR) techniques, we determined the frequency of occurrence and the proportion of mtDNA with the 4977-bp deletion in human spermatozoa with different motilities. Human spermatozoa were separated by self-migration in Percoll gradients into five fractions with different motility scores. The highest frequency of occurrence of the 4977-bp mtDNA deletion was found in sperm in the fraction with the lowest motility. The results revealed a negative correlation between sperm motility and the proportion of 4977-bp-deleted mtDNA. Furthermore, we found a significantly higher incidence of the 4977-bp mtDNA mutation in patients with asthenospermia, oligospermia, and primary infertility compared to normal individuals. These findings suggest that mtDNA mutations may play an important role in some pathophysiological conditions in human spermatozoa.
Biology of Reproduction, 1995
The accumulation of mitochondrial DNA (mtDNA) mutations has been suggested to be an important contributor to human aging and degenerative diseases. In previous studies, we found an age-dependent increase of mtDNA mutations in various human tissues. Sperm motility is one of the determinants of male fertility. The possible relationship between mtDNA deletions and diminished fertility and motility of sperm was explored in the present study. We examined accumulation of the 4977-bp mtDNA deletion in spermatozoa obtained from patients with infertility or subfertility and compared these values with those of normal individuals. Using polymerase chain reaction (PCR) techniques, we determined the frequency of occurrence and the proportion of mtDNA with the 4977-bp deletion in human spermatozoa with different motilities. Human spermatozoa were separated by self-migration in Percoll gradients into five fractions with different motility scores. The highest frequency of occurrence of the 4977-bp mtDNA deletion was found in sperm in the fraction with the lowest motility. The results revealed a negative correlation between sperm motility and the proportion of 4977-bp-deleted mtDNA. Furthermore, we found a significantly higher incidence of the 4977-bp mtDNA mutation in patients with asthenospermia, oligospermia, and primary infertility compared to normal individuals. These findings suggest that mtDNA mutations may play an important role in some pathophysiological conditions in human spermatozoa.
Male infertility and mitochondrial DNA
Biochemical and Biophysical Research Communications, 2004
The mitochondrial machinery plays a key role in the energy production and maintenance of spermatozoa motility. In this paper 200 idiopathic oligo-asthenozoospermic patients were classified on the basis of rapid progressive motility (''a'') and sperm concentration. Mitochondrial enzymatic activity was studied and correlated to the viability of sperm cells. Mitochondrial DNA purified from both motile and non-motile sperm of the same individuals was amplificated using PCR. Results suggested that only motile sperm have organelles functional in oxygen consumption, unequivocally demonstrating that motility depends on the mitochondrial activity. Mitochondrial DNA of oligo-asthenozoospermic patients seemed to present some defects that made DNA unavailable for amplification.
Oxidative stress and sperm mitochondrial DNA mutation in idiopathic oligoasthenozoospermic men
Indian journal of biochemistry & biophysics, 2009
Physiological function of reactive oxygen species (ROS) has been known since a long, but recently toxic effects of ROS on spermatozoa have gained much importance in male infertility. Mitochondrial DNA (mtDNA) is believed to be both source and target of ROS. mtDNA unlike nuclear DNA is not compactly packed and hence more susceptible to oxidative stress (OS) than nuclear DNA. In the present study, the role of OS in mitochondrial genome changes was studied in men with idiopathic infertility. The study included 33 infertile oligo-asthenozoospermic (OA) men and 30 fertile controls. Semen analyses were performed and OS was measured by estimating the level of malondialdehye (MDA) in the seminal plasma and ROS in the sperm. Sperm mtDNA was sequenced by standard PCR-DNA sequencing protocol for ATPase and nicotinamide adenine dinucleotide dehydrogenase (ND) groups of genes. Sperm count and progressive motility were found to be significantly lower in infertile group than the fertile controls. ...
2015
4To whom correspondence should be addressed Sperm motility is one of the major determinants of male fertility and is required for successful fertilization. In a previous study, we demonstrated that the occurrence and accumulation of the 4977 bp deletion of mitochondrial DNA (mtDNA) is associated with diminished fertility and motility of human spermatozoa. The possible relationship between multiple deletions of mtDNA and the decline of fertility and motility in human spermatozoa was further explored in 36 subjects including subfertile and infertile males in this study. Using long-range polymerase chain reaction (PCR), we confirmed the 4977 bp deletion and identified two novel deletions of 7345 and 7599 bp of mtDNA in the spermatozoa with poor motility. We used Percoll gradients to fractionate spermatozoa with differing motility, and then screened for two novel large-scale deletions of the mtDNA. The results showed that the ratio of the deleted mtDNA in the spermatozoa with poor motil...