Functional association between telomeres, oxidation and mitochondria

Moustakli, Efthalia; Zikopoulos, Athanasios; Sakaloglou, Prodromos; Bouba, Ioanna; Sofikitis, Nikolaos; Georgiou, Ioannis

doi:10.3389/frph.2023.1107215

Cited by 11 publications

(11 citation statements)

References 137 publications

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“…This investigation into the relationship between relative TL and mitochondrial DNA content has shed light on the complex interactions between these two vital aspects of cellular health and aging [49]. The findings highlight the significance of preserving mitochondrial health and telomere integrity as critical elements in promoting lifespan and general wellbeing, even though further study is required to clarify the specific nature of this link.…”

Section: Discussionmentioning

confidence: 91%

“…It is widely acknowledged that mtDNA is especially prone to cumulative mutation and deletion, either as a result of its proximity to the respiratory chains, which produce ROS, or because it lacks protective histones [48]. Oxidative insults are known to affect both nuclear and mitochondrial DNA [49]. A body of evidence has been gathered demonstrating that telomerase can also function in telomere-independent ways and that, under OS, the TERT transfers between the nucleus and mitochondria, and the TERC is processed, imported into mitochondria, and exported back to the cytosol [18].…”

Section: Discussionmentioning

confidence: 99%

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Association of Obesity with Telomere Length in Human Sperm

Moustakli,

Zikopoulos,

Skentou

et al. 2024

JCM

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Background: Telomere attrition and mitochondrial dysfunction are two fundamental aspects of aging. Calorie restriction (CR) is the best strategy to postpone aging since it can enhance telomere attrition, boost antioxidant capacity, and lower the generation of reactive oxygen species (ROS). Since ROS is produced by mitochondria and can readily travel to cell nuclei, it is thought to be a crucial molecule for information transfer between mitochondria and cell nuclei. Important variables that affect the quality and functionality of sperm and may affect male reproductive health and fertility include telomere length, mitochondrial content, and the ratio of mitochondrial DNA (mtDNA) to nuclear DNA (nDNA). Telomere damage results from mitochondrial failure, whereas nuclear DNA remains unaffected. This research aims to investigate potential associations between these three variables and how they might relate to body mass index. Methods: Data were collected from 82 men who underwent IVF/ICSI at the University Hospital of Ioannina’s IVF Unit in the Obstetrics and Gynecology Department. Evaluations included sperm morphology, sperm count, sperm motility, and participant history. To address this, male participants who were categorized into three body mass index (ΒΜΙ) groups—normal, overweight, and obese—had their sperm samples tested. Results: For both the normal and overweight groups, our results show a negative connection between relative telomere length and ΒΜI. As an illustration of a potential connection between mitochondrial health and telomere maintenance, a positive correlation was found for the obese group. Only the obese group’s results were statistically significant (p < 0.05). More evidence that longer telomeres are associated with lower mitochondrial content can be found in the negative connection between telomere length and mitochondrial content in both the normal and overweight groups. However, the obese group showed a positive association. The data did not reach statistical significance for any of the three groups. These associations may affect sperm quality since telomere length and mitochondrial concentration are indicators of cellular integrity and health. Moreover, the ratio of mtDNA to nDNA was positively correlated with the relative telomere lengths of the obese group, but negatively correlated with the normal and overweight groups. In every group that was studied, the results were not statistically significant. According to this, male fertility may be negatively impacted by an imbalance in the copy number of the mitochondrial genome compared to the nuclear DNA in sperm. Conclusions: Essentially, the goal of our work is to determine whether mitochondria and telomere length in human sperm interact. Understanding these connections may aid in the explanation of some male infertility causes and possibly contribute to the creation of new treatment modalities for problems pertaining to reproductive health. The functional implications of these connections and their applications in therapeutic settings require further investigation.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Association of Obesity with Telomere Length in Human Sperm

Moustakli,

Zikopoulos,

Skentou

et al. 2024

JCM

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is widely acknowledged that mtDNA is especially prone to cumulative mutation and deletion, either as a result of its proximity to the respiratory chains, which produce reactive oxygen species or because it lacks protective histones. Oxidative insults are known to affect both nuclear and mitochondrial DNA [47].…”

Section: Discussionmentioning

confidence: 99%

Associations Between Mitochondrial Content, Telomere Length, and mtDNA to nDNA Ratio in Human Sperm: Relevance to Reproductive Health

Moustakli,

Zikopoulos,

Skentou

et al. 2023

Preprint

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Important variables that affect the quality and functionality of sperm and may affect male reproductive health and fertility include telomere length, mitochondrial content, and the ratio of mitochondrial DNA (mtDNA) to nuclear DNA (nDNA). The purpose of this study was to look at the connections between these three sperm characteristics and how they might affect a woman's ability to conceive. Methods: Data were collected from 82 men who underwent IVF/ICSI at the University Hospital of Ioannina's IVF Unit in the Obstetrics and Gynecology Department. Evaluations included sperm morphology, sperm count, sperm motility, and participant history. To address this, males of reproductive age who were categorized into three body mass index (ΒΜΙ) groups—normal, overweight, and obese—had their sperm samples tested. Results: Our findings indicate a negative correlation between relative telomere length and ΒΜΙ for both the normal and overweight groups. Conversely, a positive correlation was observed for the obese group, indicating a possible relationship between mitochondrial health and telomere maintenance. The results were statistically significant only for the obese group. Furthermore, a negative correlation was observed between telomere length and mitochondrial content in both the normal and overweight groups, indicating that a lower mitochondrial content may be linked to longer telomeres. Nonetheless, there was a positive correlation for the group that was obese. For all three groups, the data did not reach statistical significance. Given that mitochondrial con-centration and telomere length are both markers of cellular integrity and health, these correla-tions may have an impact on the quality of sperm. Furthermore, the relative telomere length of the normal and overweight groups had a negative correlation with the ratio of mtDNA to nDNA, though the obese group showed a positive correlation. The findings were not statistical-ly significant in any of the groups under investigation. According to this, male fertility may be negatively impacted by an imbalance in the copy number of the mitochondrial genome com-pared to the nuclear DNA in sperm. Conclusions: Our research, in essence, emphasizes the interaction among human sperm telo-mere length, mitochondrial concentration, and the mtDNA to nDNA ratio. Gaining knowledge of these correlations could help explain the reasons behind male infertility and open up new treatment options for reproductive health problems. The functional importance of these correla-tions and possible uses in therapeutic contexts require more investigation.

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“…Telomeres are important non-coding nucleotide sequences (TTAGGG) involved in the maintenance of the genomic organization that have essential roles in maintaining genomic integrity and chromosomal stability [227]. Therefore, shortened telomeres are indicators of aging, cancer and reproductive dysfunctions [228][229][230]. If telomeres are critically shortened, chromosomes become unprotected, and cells are destined to age [231].…”

Section: Leukocytospermia and Seminal Oxidative Stressmentioning

confidence: 99%

Leukocytospermia and/or Bacteriospermia: Impact on Male Infertility

Henkel

2024

JCM

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Infertility is a globally underestimated public health concern affecting almost 190 million people, i.e., about 17.5% of people during their lifetime, while the prevalence of male factor infertility is about 7%. Among numerous other causes, the prevalence of male genital tract infections reportedly ranges between 10% and 35%. Leukocytospermia is found in 30% of infertile men and up to 20% in fertile men. Bacterial infections cause an inflammatory response attracting leukocytes, which produce reactive oxygen species (ROS) and release cytokines, both of which can cause damage to sperm, rendering them dysfunctional. Although leukocytospermia and bacteriospermia are both clinical conditions that can negatively affect male fertility, there is still debate about their impact on assisted reproduction outcomes and management. According to World Health Organization (WHO) guidelines, leukocytes should be determined by means of the Endtz test or with monoclonal antibodies against CD15, CD68 or CD22. The cut-off value proposed by the WHO is 1 × 106 peroxidase-positive cells/mL. For bacteria, Gram staining and semen culture are regarded as the “gold standard”, while modern techniques such as PCR and next-generation sequencing (NGS) are allowing clinicians to detect a wider range of pathogens. Whereas the WHO manual does not specify a specific value as a cut-off for bacterial contamination, several studies consider semen samples with more than 103 colony-forming units (cfu)/mL as bacteriospermic. The pathogenic mechanisms leading to sperm dysfunction include direct interaction of bacteria with the male germ cells, bacterial release of spermatotoxic substances, induction of pro-inflammatory cytokines and ROS, all of which lead to oxidative stress. Clinically, bacterial infections, including “silent” infections, are treatable, with antibiotics being the treatment of choice. Yet, non-steroidal antiphlogistics or antioxidants should also be considered to alleviate inflammatory lesions and improve semen quality. In an assisted reproduction set up, sperm separation techniques significantly reduce the bacterial load in the semen. Nonetheless, contamination of the semen sample with skin commensals should be prevented by applying relevant hygiene techniques. In patients where leukocytospermia is detected, the causes (e.g. infection, inflammation, varicocele, smoking, etc.) of the leukocyte infiltration have to be identified and addressed with antibiotics, anti-inflammatories or antioxidants in cases where high oxidative stress levels are detected. However, no specific strategy is available for the management of leukocytospermia. Therefore, the relationship between bacteriospermia and leukocytospermia as well as their specific impact on functional sperm parameters and reproductive outcome variables such as fertilization or clinical pregnancy must be further investigated. The aim of this narrative review is to provide an update on the current knowledge on leukocytospermia and bacteriospermia and their impact on male fertility.

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Functional association between telomeres, oxidation and mitochondria

Cited by 11 publications

References 137 publications

Association of Obesity with Telomere Length in Human Sperm

Association of Obesity with Telomere Length in Human Sperm

Associations Between Mitochondrial Content, Telomere Length, and mtDNA to nDNA Ratio in Human Sperm: Relevance to Reproductive Health

Leukocytospermia and/or Bacteriospermia: Impact on Male Infertility

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