A Systematic Review of the Impact of Mitochondrial Variations on Male Infertility

Amor, Houda; Hammadeh, Mohamad Eid

doi:10.3390/genes13071182

Cited by 9 publications

(5 citation statements)

References 117 publications

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“…At present, some high-incidence single nucleotide substitutions in sperm mtDNA are considered to be related to male infertility. 5,45 However, these studies were unable to exclude some high-frequency somatic muta-tions, making their results less reliable. Our ingenious design could avoid this problem, providing direct evidence that O/A/T patients carry more pathogenic mutations and VUS-As.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, we hypothesized that the impairment of the mitochondrial function caused by pathogenic mutations and VUS‐As is the cause of the decreased semen quality. At present, some high‐incidence single nucleotide substitutions in sperm mtDNA are considered to be related to male infertility 5,45 . However, these studies were unable to exclude some high‐frequency somatic mutations, making their results less reliable.…”

Section: Discussionmentioning

confidence: 99%

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Increases in computationally predicted deleterious variants of unknown significance and sperm mtDNA copy numbers may be associated with semen quality

Pi,

Huang,

et al. 2023

Andrology

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BackgroundMitochondria are essential for sperm motility because they provide the energy required for the movement. Changes in sperm mtDNA, such as point mutations, large‐scale deletions, or copy number variations, may interfere with ATP production and reduce sperm motility. However, it is not clear if changes in mtDNA are linked to semen quality.ObjectivesTo explore the association between sperm mitochondrial DNA (mtDNA) changes and semen quality.Materials and methodsSixty‐five oligo and/or astheno and/or terato patients (O/A/T) patients and 41 controls were recruited from couples undergoing assisted reproduction. Semen and blood samples were collected from the same individual on the day of oocyte retrieval to extract, isolate and purify mtDNA for next‐generation sequencing. mtDNA copy numbers were assessed in 64 patient and 39 control sperm DNA samples using quantitative real‐time PCR. The 4977 bp deletion was assessed in 20 patient and 20 control sperm DNA samples using polymerase chain reaction.ResultsThe mtDNA of patients was more likely to carry pathogenic variants or variants of unknown significance (VUSs) (P = 0.091) with higher heteroplasmy levels (P < 0.05) than that of controls. Interestingly, 33.85% of O/A/T patients (22 out of 65) lacked unique variants in their spermatozoa. but presented an exceptionally high mtDNA copy number (P < 0.0001). Moreover, we observed a decrease in the heteroplasmy level of common mtDNA variants shared by somatic and gamete cells (P < 0.0001) and the emergence of a very large number of de novo mtDNA variants with low‐level heteroplasmy in spermatozoa.Discussion and conclusionThe increases in the number of computationally predicted deleterious VUS and mtDNA copies in spermatozoa may be associated with semen quality. Exposure to environmental mutation pressure that causes novel mtDNA variants with low‐level heteroplasmy may occur during spermatogenesis. Furthermore, when a certain harmful threshold is reached, male germ cells may degrade mtDNA with mutations and replicate the correct mtDNA sequence to maintain the mitochondrial function in spermatozoa.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Increases in computationally predicted deleterious variants of unknown significance and sperm mtDNA copy numbers may be associated with semen quality

Pi,

Huang,

et al. 2023

Andrology

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“…They are required for natural conception and in vitro fertilization. The mitochondrial DNA mutation could be one cause of male infertility [49][50][51]. Mitochondrial DNA is vulnerable to damage from reactive oxygen species due to the lack of histone protein.…”

Section: Mitochondrial Dna Mutationmentioning

confidence: 99%

Semen Analysis and Infertility

Mongkolchaipak¹

2023

IVF Technologies and Infertility - Current Practices and New Perspectives

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Male factor infertility contribute approximately at 50% for the cause of infertility. The steady declination of semen quality in men for all over the world might be from various factors such as life style changes, environmental toxicity, dietary contribution and social problems. Assisted reproduction is the main treatment of choice for male infertility; However, in severe male factor infertility, the treatment outcomes could end up with recurrent implantation failure or recurrent pregnancy loss. Basic semen analysis still has limitation to explain the cause of failure for the part of male factors. The purposes of developing new sperm evaluation methods are to improve the diagnostic tools for identifying the sperm defects, appraise of fertility potential and provide suitable treatment for an infertile couple, explain the cause of treatment failure from male factor part and measure the efficacy of male contraception.

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“…Although they are relatively uncommon, mitochondrial-associated problems that can impair male fertility can have a serious effect on male reproductive health [7]. Sperm motility issues, low sperm counts, oxidative stress, asthenozoospermia, genetic mitochondrial abnormalities, and age-related decline are a few mitochondrial-related problems that may lead to male infertility [8].…”

Section: Introductionmentioning

confidence: 99%

Sperm Mitochondrial Content and Mitochondrial DNA to Nuclear DNA Ratio Are Associated with Body Mass Index and Progressive Motility

Moustakli,

Zikopoulos,

Skentou

et al. 2023

Biomedicines

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Background: Mitochondrial dysfunction is a risk factor in the pathogenesis of metabolic disorders. According to the energy requirements, oxidative phosphorylation and the electron transport chain work together to produce ATP in sufficient quantities in the mitochondria of eukaryotic cells. Abnormal mitochondrial activity causes fat accumulation and insulin resistance as cells require a balance between the production of ATP by oxidative phosphorylation (OXPHOS) in the mitochondria and the dissipation of the proton gradient to reduce damage from reactive oxygen species (ROS). This study aims to explore the relationship between the mitochondrial content of sperm and the ratio of mitochondrial DNA to nuclear DNA in relation to body mass index (BMI) and how it may affect the progressive motility of sperm cell. Understanding the relationships between these important variables will help us better understand the possible mechanisms that could connect sperm motility and quality to BMI, as well as further our understanding of male fertility and reproductive health. Methods: Data were collected from 100 men who underwent IVF/ICSI at the University Hospital of Ioannina’s IVF Unit in the Obstetrics and Gynecology Department. The body mass index (BMI) of the males tested was used to classify them as normal weight; overweight; and obese. Evaluations included sperm morphology; sperm count; sperm motility; and participant history. Results: In the group of men with normal BMI, both BMI and progressive motility displayed a statistically significant association (p < 0.05) with mitochondrial DNA content, relative mitochondrial DNA copy number, and the mtDNA/nDNA ratio. Similar to this, there was a positive association between BMI and motility in the groups of men who were overweight and obese, as well as between the expression of mitochondrial DNA and the mtDNA/nDNA ratio, with statistically significant differences (p < 0.05). There was not a statistically significant difference observed in the association between the relative mtDNA copy number and BMI or motility for the overweight group. Finally, the relative mtDNA copy number in the obese group was only associated with motility (p = 0.034) and not with BMI (p = 0.24). Conclusions: We found that in all three groups, BMI and progressive motility exhibited comparable relationships with mitochondrial DNA expression and the mtDNA/nDNA ratio. However, only in the normal group and in the obese group, the relative mitochondrial DNA copy number showed a positive association with BMI and progressive motility.

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A Systematic Review of the Impact of Mitochondrial Variations on Male Infertility

Cited by 9 publications

References 117 publications

Increases in computationally predicted deleterious variants of unknown significance and sperm mtDNA copy numbers may be associated with semen quality

Increases in computationally predicted deleterious variants of unknown significance and sperm mtDNA copy numbers may be associated with semen quality

Semen Analysis and Infertility

Sperm Mitochondrial Content and Mitochondrial DNA to Nuclear DNA Ratio Are Associated with Body Mass Index and Progressive Motility

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