Mitochondrial Deoxyribonucleic Acid 4977-bp Deletion is Associated with Diminished Fertility and Motility of Human Sperm1 (original) (raw)
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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.
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...
Molecular Human Reproduction, 1998
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 motility and diminished fertility were significantly higher than those in the spermatozoa with good motility and fertility. In addition, we found that the frequencies of the three large-scale deletions in the spermatozoa from patients with primary infertility and oligoasthenozoospermia were higher than those of the fertile males. Our findings suggest that mtDNA deletions may play an important role in some pathophysiological conditions of human spermatozoa.
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
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...
Mitochondrial DNA mutations in etiopathogenesis of male infertility
Indian Journal of Urology, 2008
Objective: Objective: To understand role of mitochondrial (mt) mutations in genes regulating oxidative phosphorylation (OXPHOS) in pathogenesis of male infertility. Infertility affects approximately 15% of couples trying to conceive. Infertility is frequently attributed to defects of sperm motility and number. Mitochondrion and mitochondrial DNA (mtDNA) play an important role in variety of physiological process. They control the oxidative energy supply and thus are central to growth, development and differentiation. Mitochondrial function is controlled by a Þ ne-tuned crosstalk between mtDNA and nuclear DNA (nDNA). As mitochondria supply energy by OXPHOS, any mutation in mtDNA disrupts adenosine triphosphate (ATP) production and thus result in an impaired spermatogenesis and impaired ß agellar movement. As sperm midpiece has few mtDNA copies, thus enhanced number of mutant mtDNA results in early phenotypic defect which manifest as spermatogenic arrest or asthenozoospermia. Oxidative stress and mtDNA mutations are positively correlated and mutations in mitochondrial genome (mt genome) are implicated in the lowered fertilising capacity of the sperm and affects the reproductive potential of an individual. Materials and Methods: Materials and Methods: A thorough review of articles in the last 15 years was cited with reference to the below-mentioned keywords. The articles considered discuss the role of mt genome in the normal functioning of sperm and the factors associated with mt mutations and impact of these mutations on the reproductive potential. Results: Results: Sperm motility is a very important factor for the fertilisation of ova. The energy requirements of sperm are therefore very critical for sperm. Mutations in the mitochondrial genes as COX II, ATPase 6 and 8 play an important role and disrupts ATP production affecting the spermatogenesis and sperm motility. Therefore, the aberrations in mt genome are an important etiopatholgy of male infertility. Conclusion: Conclusion: In the context of male infertility, mt mutations, generation of reactive oxygen species and lowered antioxidant capacity are interlinked and constitute a uniÞ ed pathogenic molecular mechanism. In the era of assisted reproduction technique (ART), it is very important to distinguish between mutations in nuclear and mitochondrial genomes in sperm, as mtDNA mutations are better diagnostic and prognostic markers in infertile men opting for ART.
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.
Journal of Human Reproductive Sciences, 2016
oxidative phosphorylation. Sperm cells are susceptible to damage from oxidants because they lack endogenous antioxidants activity. [3] The molecular studies have revealed that mitochondrial genes ATPase 6, ATPase 8, COX 3, COX 2, CytB, ND3, ND4, ND5, and ND6 involved the formation of mature sperm and rapid flagellar movement after ejaculation. [4] The oxidative phosphorylation in mitochondria is essential for sperm ABSTRACT OBJECTIVE: To determine the association of large-scale mitochondrial DNA (mtDNA) deletions with abnormal sperm or abnormal flagellar movement of human spermatozoa in asthenozoospermia and oligoasthenoteratozoospermia (OAT) subjects using percoll gradients fractionation and long-range polymerase chain reaction (PCR). DESIGN: We investigated sixty infertile men and thirty normal healthy fertile controls. Of sixty infertile men, 39 were asthenozoospermia and 21 were OAT. MATERIALS AND METHODS: Percoll gradients discontinuous technique was used for separation of spermatozoa on the basis of their motility. Long-range PCR was used for detection of "common" 4977-bp deletions, and primer shift technique was used for confirmation of deletions. RESULTS: Overall fourteen subjects (14/60; 23.3%) of which eight (8/39; 20.5%) asthenozoospermia and six (6/21; 28.6%) OAT had shown deletions of 4977-bp. Deletions were more common (23.3%) in 40% fraction than 60% (11.6%) and 80% (5%) fractions. Sequencing results had shown deleted region of mtDNA. CONCLUSION: Abnormal spermatozoa had more number of mtDNA deletions than normal sperm, and abnormal spermatozoa had lost genes for the oxidative phosphorylation. Our findings suggest that large-scale 4977-bp mtDNA deletions in the spermatozoa from the infertile subjects cause the asthenozoospermic and OAT pathophysiological conditions in infertile males.
Sperm mitochondrial DNA depletion in men with asthenospermia
Fertility and Sterility, 2004
Objective: To determine the content of sperm mitochondrial DNA (mtDNA) in patients with asthenospermia or with poor sperm motility. Design: Analysis of the content of mtDNA as the ratio between the amount of mtDNA and nuclear DNA by using a new concurrent polymerase chain reaction. Setting: University hospital infertility center. Patient(s): Eighty-six men who sought infertility therapy. Intervention(s): Moving characteristics of sperm were examined with a computer-assisted semen analyzer. Main Outcome Measure(s): Sperm samples were classified into two groups, one with asthenospermia and the other with normal moving characteristics. The content of mtDNA in sperm was determined by polymerase chain reaction. We analyzed the mitochondrial mass by MitoTracker Green staining and analyzed DNA content with propidium iodide staining by flow cytometry. Result(s): A decrease in sperm mtDNA content was detected in patients with asthenospermia or with poor sperm motility (Ͻ20% motility). The relative mtDNA contents in the asthenospermia and normal groups were 7.2 Ϯ 1.3 (mean Ϯ SD, n ϭ 23) and 74.1 Ϯ 2.0 (n ϭ 29), respectively. Lower intensities of propidium iodide staining were detected in patients with asthenospermia or poor motility, but there was no significant difference in MitoTracker Green staining between the sperm with different motility. Conclusion(s): We suggest that mtDNA content may serve as a useful indicator of sperm quality and that mtDNA depletion may play an important role in the pathophysiology of some male infertility.
Mitochondrial DNA Content of Human Spermatozoa1
Biology of Reproduction, 2003
Sperm mitochondria play an important role in spermatozoa because of the high ATP demand of these cells. Different mitochondrial DNA (mtDNA) mutations and haplogroups influence sperm function. The mtDNA dose also contributes to genetic variability and pathology in different tissues and organs, but nothing is known about its relevance in the performance of spermatozoa. We estimated the variability in mtDNA content within a population of men. Different mtDNA:nuclear DNA ratios were characteristic of progressive and nonprogressive spermatozoa, confirming the influence of mtDNA content on sperm functionality. We also estimated that the absolute content of mtDNA was 700 and 1200 mtDNA copies per cell in progressive and nonprogressive human spermatozoa, respectively. These results suggest that a marked increase of mtDNA copy number per cell volume takes place during spermatogenesis.