Telomere length in reproduction

Thilagavathi, Jayapalraja; Venkatesh, S.; Dada, Rima

doi:10.1111/and.12008

Cited by 82 publications

(72 citation statements)

References 149 publications

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“…They also found that sperm telomere length is related to sperm count, being lower in oligozoospermic than in normozoospermic men. These results confirmed the findings of Thilagavathi et al [74] which reported shorter sperm telomere length in men with idiopathic infertility in comparison with controls [74]. Therefore, the number of studies linking infertility and low sperm count to shorter sperm telomere length is limited, and the question whether shorter sperm telomere length is the cause of infertility (through increased apoptosis of germ cells, impaired spermatogenesis, and reduced sperm count) or a marker of damaged spermatogenesis is yet to be answered by future studies.…”

Section: Telomere Lengthsupporting

confidence: 93%

The Impact of Aging on Fertility: Similarities and Differences between Ovaries and Testes

Albu¹,

Albu²

2017

Testes and Ovaries - Functional and Clinical Differences and Similarities

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The increasing age seems to have a negative impact on reproductive functions not only in women but also in men. Therefore, our aim was to review the data available in the literature regarding the impact of advancing age on fertility and the mechanisms underlying this association in both genders. The available data suggest that the effects of age on ovarian function cause a decrease in fertility starting 13 years before menopause. Statistics show that 10% of women will have a decreased fertility starting with the age of 30. The impact of age on ovary is due to both decreased number and quality of the oocytes, resulting in a high rate of chromosomal aneuploidy in the embryo and mitochondria dysfunction. Assisted reproductive technologies aiming to identify competent embryo were created but for the moment the results are unsatisfactory. On the other hand, in men, the semen quality and testicular function were found to gradually decrease with age and most of the studies also describe a negative impact on fertility. The mechanisms underlying decreased fertility are mainly genetic and epigenetics changes. However, if the effects of age on male fertility in men can be overcome by assisted reproductive technologies is not clear yet as the results of the studies are inconsistent.

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Section: Telomere Lengthsupporting

confidence: 93%

The Impact of Aging on Fertility: Similarities and Differences between Ovaries and Testes

Albu¹,

Albu²

2017

Testes and Ovaries - Functional and Clinical Differences and Similarities

View full text Add to dashboard Cite

show abstract

“…In fact, the STL plays a critical role in meiosis, and compromised telomere length in sperm may contribute to segregation errors, apoptosis with reduced sperm count and reduced fertility3945. In addition, many factors commonly implicated in spermatogenesis and male infertility such as oxidative stress, infections, smoking and obesity, might be implicated in telomere shortening46. The pathophysiological relationship between STL, sperm DNA fragmentation and ROS is intriguing.…”

Section: Discussionmentioning

confidence: 99%

Semen preparation methods and sperm telomere length: density gradient centrifugation versus the swim up procedure

Zhao

Yang

Sheng

et al. 2016

Sci Rep

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Previous studies have shown that both density gradient centrifugation (DGC) and swim up (SU) procedures can select spermatozoa with longer telomeres for assisted reproduction techniques (ART). However, it is unknown which approach is more effective. The aim of the present study was to compare the effects of these two methods on sperm telomere length (STL). A total of 150 normozoospermic subjects were recruited. STL, DNA fragmentation index (DFI), reactive oxygen species (ROS) content and progressive motility of semen samples were detected before and after the procedures of DGC and SU. When compared to raw semen, the average length of sperm telomeres was significantly longer after the two sperm preparation methods. However, no significant difference was found between the DGC and SU procedures. We also found that semen prepared by the two methods had lower DNA fragmentation, ROS content and sperm progressive motility. However, no significant difference was found in those parameters between the two procedures. This is the first study that compares the effects of the DGC and SU procedures on STL, and the results show that both methods can recover a sperm population with longer STL and better DNA integrity for ART.

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“…In adult somatic cells, telomeres are composed of large noncoding sequences of approximately 1000–2000 TTAGGG tandem base pair repeats that end in a 3′ extension past the 5′ terminus [2]. In other select cells, the telomeres are maintained and can be considerably longer, such as adult human germ cells which can contain anywhere from 500–5000 repeats [3,4,5]. During each cycle of cell division telomeres are incompletely replicated, and consequently, their ends are progressively shortened [6].…”

Section: Introductionmentioning

confidence: 99%

Treating Cancer by Targeting Telomeres and Telomerase

et al. 2017

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Telomerase is expressed in more than 85% of cancer cells. Tumor cells with metastatic potential may have a high telomerase activity, allowing cells to escape from the inhibition of cell proliferation due to shortened telomeres. Human telomerase primarily consists of two main components: hTERT, a catalytic subunit, and hTR, an RNA template whose sequence is complimentary to the telomeric 5′-dTTAGGG-3′ repeat. In humans, telomerase activity is typically restricted to renewing tissues, such as germ cells and stem cells, and is generally absent in normal cells. While hTR is constitutively expressed in most tissue types, hTERT expression levels are low enough that telomere length cannot be maintained, which sets a proliferative lifespan on normal cells. However, in the majority of cancers, telomerase maintains stable telomere length, thereby conferring cell immortality. Levels of hTERT mRNA are directly related to telomerase activity, thereby making it a more suitable therapeutic target than hTR. Recent data suggests that stabilization of telomeric G-quadruplexes may act to indirectly inhibit telomerase action by blocking hTR binding. Telomeric DNA has the propensity to spontaneously form intramolecular G-quadruplexes, four-stranded DNA secondary structures that are stabilized by the stacking of guanine residues in a planar arrangement. The functional roles of telomeric G-quadruplexes are not completely understood, but recent evidence suggests that they can stall the replication fork during DNA synthesis and inhibit telomere replication by preventing telomerase and related proteins from binding to the telomere. Long-term treatment with G-quadruplex stabilizers induces a gradual reduction in the length of the G-rich 3’ end of the telomere without a reduction of the total telomere length, suggesting that telomerase activity is inhibited. However, inhibition of telomerase, either directly or indirectly, has shown only moderate success in cancer patients. Another promising approach of targeting the telomere is the use of guanine-rich oligonucleotides (GROs) homologous to the 3’ telomere overhang sequence (T-oligos). T-oligos, particularly a specific 11-base oligonucleotide (5’-dGTTAGGGTTAG-3’) called T11, have been shown to induce DNA damage responses (DDRs) such as senescence, apoptosis, and cell cycle arrest in numerous cancer cell types with minimal or no cytostatic effects in normal, non-transformed cells. As a result, T-oligos and other GROs are being investigated as prospective anticancer therapeutics. Interestingly, the DDRs induced by T-oligos in cancer cells are similar to the effects seen after progressive telomere degradation in normal cells. The loss of telomeres is an important tumor suppressor mechanism that is commonly absent in transformed malignant cells, and hence, T-oligos have garnered significant interest as a novel strategy to combat cancer. However, little is known about their mechanism of action. In this review, we discuss the current understanding of how T-oligos exert their antiproliferative effe...

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Telomere length in reproduction

Cited by 82 publications

References 149 publications

The Impact of Aging on Fertility: Similarities and Differences between Ovaries and Testes

The Impact of Aging on Fertility: Similarities and Differences between Ovaries and Testes

Semen preparation methods and sperm telomere length: density gradient centrifugation versus the swim up procedure

Treating Cancer by Targeting Telomeres and Telomerase

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