Littérature scientifique sur le sujet « Sperm telomere length »

Over the past decade, telomeres have attracted increasing attention due to the role they play in human fertility. However, conflicting results have been reported on the possible association between sperm telomere length (STL) and leukocyte telomere length (LTL) and the quality of the sperm parameters. The aim of this study was to run a comprehensive study to investigate the role of STL and LTL in male spermatogenesis and infertility. Moreover, the association between the sperm parameters and 11 candidate single nucleotide polymorphisms (SNPs), identified in the literature for their association with telomere length (TL), was investigated. We observed no associations between sperm parameters and STL nor LTL. For the individual SNPs, we observed five statistically significant associations with sperm parameters: considering a p < 0.05. Namely, ACYP2˗rs11125529 and decreased sperm motility (p = 0.03); PXK˗rs6772228 with a lower sperm count (p = 0.02); NAF1˗rs7675998 with increased probability of having abnormal acrosomes (p = 0.03) and abnormal flagellum (p = 0.04); ZNF208˗rs8105767 and reduction of sperms with normal heads (p = 0.009). This study suggests a moderate involvement of telomere length in male fertility; however, in our analyses four SNPs were weakly associated with sperm variables, suggesting the SNPs to be pleiotropic and involved in other regulatory mechanisms independent of telomere homeostasis, but involved in the spermatogenic process.

In recent decades, male infertility has been correlated with the shortening of sperm telomeres. Telomeres regulate the reproductive lifespan by mediating the synapsis and homologous recombination of chromosomes during gametogenesis. They are composed of thousands of hexanucleotide DNA repeats (TTAGGG) that are coupled to specialized shelterin complex proteins and non-coding RNAs. Telomerase activity in male germ cells ensures that the telomere length is maintained at maximum levels during spermatogenesis, despite telomere shortening due to DNA replication or other genotoxic factors such as environmental pollutants. An emerging body of evidence has associated an exposure to pollutants with male infertility. Although telomeric DNA may be one of the important targets of environmental pollutants, only a few authors have considered it as a conventional parameter for sperm function. The aim of this review is to provide comprehensive and up-to-date data on the research carried out so far on the structure/function of telomeres in spermatogenesis and the influence of environmental pollutants on their functionality. The link between pollutant-induced oxidative stress and telomere length in germ cells is discussed.

Telomere length has attracted much interest as a topic of study in human reproduction; furthermore, the link between sperm telomere length and fertility outcomes has been investigated in other species. This biomarker, however, has not been much explored in other animals, such as pigs, and whether it is related to sperm quality and fertility outcomes remains unknown. The present work aimed to determine the absolute value of telomere length in pig sperm, as well as its relationship to sperm quality parameters and embryo development. Telomere length was determined through quantitative fluorescence in situ hybridization (qFISH) in 23 pig sperm samples and data were correlated to quality parameters (motility, morphology, and viability) and in vitro fertilization outcomes. We found that the mean telomere length in pig sperm was 22.1 ± 3.6 kb, which is longer than that previously described in humans. Whilst telomere length was not observed to be correlated to sperm quality variables (p > 0.05), a significant correlation between telomere length and the percentage of morulae 6 days after in vitro fertilization was observed (rs = 0.559; 95% C.I. = (−0.007 to 0.854); p = 0.047). Interestingly, this correlation was not found when percentages of early blastocysts/blastocysts (rs = 0.410; 95% C.I. = (−0.200 to 0.791); p = 0.164) and of hatching/hatched blastocysts (rs = 0.356; 95% C.I. = (− 0.260 to 0.766); p = 0.233) were considered. Through the separation of the samples into two groups by the median value, statistically significant differences between samples with shorter telomeres than the median and samples with longer telomeres than the median were found regarding development to morula (11.5 ± 3.6 vs. 21.8 ± 6.9, respectively) and to early blastocyst/blastocysts (7.6 ± 1.4 vs. 17.9 ± 12.2, respectively) (p < 0.05). In the light of these results, sperm telomere length may be a useful biomarker for embryo development in pigs, as sperm with longer telomeres lead to higher rates of morulae and blastocysts.

Telomeres promote genome integrity by protecting chromosome ends from the activation of the DNA damage response and protecting chromosomes from the loss of coding sequences due to the end replication problem. Telomere length (TL) is progressively shortened as age progresses, thus resulting in cellular senescence. Therefore, TL is in strong adverse linear correlation with aging. Mounting evidence supports the notion that telomeres and male/female infertility are in a close relationship, posing the biology of telomeres as a hot topic in the era of human-assisted reproduction. Specifically, the length of sperm telomeres is gradually increasing as men get older, while the telomere length of the oocytes seems not to follow similar patterns with that of sperm. Nonetheless, the telomere length of the embryos during the cleavage stages seems to have a paternal origin, but the telomere length can be further extended by telomerase activity during the blastocyst stage. The latter has been proposed as a new molecular biomarker with strong predictive value regarding male infertility. As far as the role of telomeres in assisted reproduction, the data is limited but the length of telomeres in both gametes seems to be affected mainly by the cause of infertility rather than the assisted reproductive therapy (ART) procedure itself. The present review aims to shed more light into the role of telomeres in human embryological parameters, including gametes and embryos and also presents opinions regarding the association between telomeres and in vitro fertilization (IVF).

Telomeres are repeating DNA found at the ends of chromosomes that, in the absence of restorative processes, shorten with cell replications and are implicated as a cause of senescence. It appears that sperm telomere length (TL) increases with age in humans, and as a result offspring of older fathers inherit longer telomeres. We review possible mechanisms underlying this paternal age at conception (PAC) effect on TL, including sperm telomere extension due to telomerase activity, age-dependent changes in the spermatogonial stem cell population (possibly driven by ‘selfish’ spermatogonia) and non-causal confounding. In contrast to the lengthening of TL with PAC, higher maternal age at conception appears to predict shorter offspring TL in humans. We review evidence for heterogeneity across species in the PAC effect on TL, which could relate to differences in statistical power, sperm production rates or testicular telomerase activity. Finally, we review the hypothesis that the PAC effect on TL may allow a gradual multi-generational adaptive calibration of maintenance effort, and reproductive lifespan, to local demographic conditions: descendants of males who reproduced at a later age are likely to find themselves in an environment where increased maintenance effort, allowing later reproduction, represents a fitness improving resource allocation. This article is part of the theme issue ‘Understanding diversity in telomere dynamics’.

A critical issue for species integrity is the existence of a telomere elongation program during embryogenesis that ensures sufficient telomere reserves in mammalian newborns. Two different mechanisms have been reported to act on telomere elongation during early embryogenesis: first, the telomerase, the ribonucleoprotein that adds telomeric repeats onto the chromosome ends, known to be responsible for the telomere lengthening at the morula-blastocyst transition in mice and bovine; second, in laboratory mice strains, mature oocytes increase the length of their relatively short telomeres between the 1-cell and 2-cell stages by a recombination or ALT-like pathway. In contrast, spermatozoa, the terminally differentiated male gametes, exhibit a very long telomere length (TL). The aim of this study was to clarify the potential role of the spermatozoa TL in the telomere lengthening occurring between oocyte and the 2-cell stage. For this purpose, we used 2 mouse species known to differ greatly in their TL [Mus musculus (hybrid C57CBAF1), long TL, and Mus spretus, short TL]. First, we compared relative TL in sperm samples from 5 age-matched males of each species by quantitative real-time PCR, with the numbers of telomere repeats being normalized, to the amount of DNA present in the sample (based on quantification of the Rn18S gene) by the comparative Ct method. Then, 1- and 2-cell embryos were produced by fertilizing Mus musculus oocytes with either Mus musculus or Mus spretus spermatozoa. The TL analysis in oocytes, zygotes, or 2-cell embryos was carried out by absolute quantification of telomere repeats by qPCR and normalized to the highest Ct observed value. Twenty to thirty samples per stage were analyzed, with each sample consisting in 2 matured oocytes, 2 zygotes, or one 2-cell embryo, to allow comparisons between stages. One-way ANOVA was used for statistical analysis. Mus spretus spermatozoa had significantly shorter telomeres than did Mus musculus (1.0 ± 0.1 v. 9.0 ± 1.5, respectively; P ≤ 0.01). The TL increased after fertilization from oocyte to zygote and 2-cell embryo stages in Mus musculus (1.0 ± 0.1, 1.5 ± 0.1, and 2.4 ± 0.2, respectively; P ≤ 0.01). In contrast, no differences were found in the TLs between the 3 stages in Mus spretus hybrids (oocyte: 1.0 ± 0.1; zygote: 1.0 ± 0.1; and 2-cell embryo: 1.0 ± 0.1), indicating that no elongation occurred after fertilization with spermatozoa with short telomeres. Herein, we demonstrated that before embryonic genome activation occurs, spermatozoa TL determines TL of the early embryo, suggesting that spermatozoon telomeres may act as recombination templates for early telomere lengthening right after syngamia.

Standardized swim-up trials are used in in vitro fertilization clinics to select particularly motile spermatozoa in order to increase the probability of a successful fertilization. Such trials demonstrate that sperm with longer telomeres have higher motility and lower levels of DNA damage. Regardless of whether sperm motility, and successful swim-up to fertilization sites, is a direct or correlational effect of telomere length or DNA damage, covariation between telomere length and sperm performance predicts a relationship between telomere length and probability of paternity in sperm competition, a prediction that for ethical reasons cannot be tested on humans. Here, we test this prediction in sand lizards ( Lacerta agilis ) using experimental data from twice-mated females in a laboratory population, and telomere length in blood from the participating lizards. Female identity influenced paternity (while the mechanism was not identified), while relatively longer male telomeres predicted higher probability of paternity. We discuss potential mechanisms underpinning this result.

Telomeres are repeat regions of DNA that cap either end of each chromosome, thereby providing stability and protection from the degradation of gene-rich regions. Each cell replication causes the loss of telomeric repeats due to incomplete DNA replication, though it is well-established that progressive telomere shortening is evaded in male germ cells by the maintenance of active telomerase. However, germ cell telomeres are still susceptible to disruption or insult by oxidative stress, toxicant exposure, and aging. Our aim was to examine the relative telomere length (rTL) in an outbred Sprague Dawley (SD) and an inbred Brown Norway (BN) rat model for paternal aging. No significant differences were found when comparing pachytene spermatocytes (PS), round spermatids (RS), and sperm obtained from the caput and cauda of the epididymis of young and aged SD rats; this is likely due to the high variance observed among individuals. A significant age-dependent decrease in rTL was observed from 115.6 (±6.5) to 93.3 (±6.3) in caput sperm and from 142.4 (±14.6) to 105.3 (±2.5) in cauda sperm from BN rats. Additionally, an increase in rTL during epididymal maturation was observed in both strains, most strikingly from 115.6 (±6.5) to 142 (±14.6) in young BN rats. These results confirm the decrease in rTL in rodents, but only when an inbred strain is used, and represent the first demonstration that rTL changes as sperm transit through the epididymis.

Male factors are suspected in around half cases of infertility, of which up to 40% are diagnosed as idiopathic. In the context of a continuously increased resort to ART and increased decline of semen parameters, it is of greatest interest to evaluate an additional potential biomarker of sperm quality. According to PRISMA guidelines, this systematic review of the literature selected studies evaluating telomere length in sperm and/or in leukocytes as a potential male fertility biomarker. Twenty-two publications (3168 participants) were included in this review of experimental evidence. For each study, authors determined if there was a correlation between telomere length and semen parameters or fertility outcomes. Of the 13 studies concerning sperm telomere length (STL) and semen parameters, ten found an association between short STL and altered parameters. Concerning the impact of STL on ART results, the data are conflicting. However, eight of the 13 included studies about fertility found significantly longer sperm telomeres in fertile men than in infertile men. In leukocytes, the seven studies reported conflicting findings. Shorter sperm telomeres appear to be associated with altered semen parameters or male infertility. Telomere length may be considered as a new molecular marker of spermatogenesis and sperm quality, and thus is related to male fertility potential. However, additional studies are needed to define the place of the STL in the assessment of individual fertility.

Telomere length (TL) in humans is highly heritable and undergoes progressive age-dependent shortening in somatic cells. By contrast, sperm donated by older men display comparatively long telomeres, presumably because in the male germline, telomeres become longer with age. This puzzling phenomenon might explain why TL in the offspring correlates positively with paternal age. The present communication proposes that mitochondrial DNA polymorphisms and heteroplasmy cause variation in the production of reactive oxygen species, which, in turn, mediate age-dependent selection of germ stem cells with long telomeres and hence sperm with long telomeres. These long telomeres are then inherited by the offspring. The effect of paternal age on the offspring TL might be an evolutionarily driven mechanism that helps regulate TL across the human population. This article is part of the theme issue ‘Understanding diversity in telomere dynamics’.

Les télomères sont des structures essentielles de la biologie des eucaryotes, participant à la réplication et à la protection du génome. Ils interagissent avec le contenu nucléaire soit directes, soit via un complexe de shelterines appelé télosome. Ils raccourcissent après la division cellulaire. Les télomères spermatiques ont des rôles et une architecture spécifiques. Organisés en doublets et quadruplets, un noyau de spermatozoïde haploïde contient entre 12 et 23 signaux détectables. Raccourcis par les divisions successives, ils font l'objet d'une restauration et d'un allongement permanents dans les cellules germinales. Leur longueur varie selon les individus et les générations, interrogeant sur les facteurs impliqués.Dans le cadre du cette thèse, nous avons étudié trois situations différentes. Premièrement, nous avons cherché à savoir si la longueur des télomères et le nombre moyen de télomères dans le noyau spermatique étaient liés au stress oxydatif et aux altérations des paramètres nucléaires parmi les hommes infertiles. Nous avons réalisé une étude prospective sur 52 hommes, avec un groupe cas de 30 hommes infertiles présentant des altérations conventionnelles des paramètres du sperme et un groupe contrôle d'hommes fertiles normozoospermiques. Le nombre moyen de télomères par tête de spermatozoïde était significativement plus élevé chez les cas (21.7 ± 4.3 versus 18.8 ± 3.0, p = 0.049) tout comme la présence d’espèces réactives de l'oxygène intracytoplasmiques et les défauts de condensation. Plus le nombre de télomères était élevé, plus il y avait de défauts de condensation de la chromatine (r = 0.29, p 0.04).Deuxièmement, nous avons évalué l'impact du cancer du testicule et de ses traitements sur les télomères spermatiques. Nous avons réalisé une étude ancillaire sur 29 patients dans le cadre d'un projet de recherche qui suivait des patients atteints de cancer du testicule avant et après chimiothérapie ou radiothérapie adjuvante. Les patients avaient un nombre plus élevé de signaux de télomères par tête de spermatozoïde que les témoins avant et après le traitement (18.1 ± 2.7 versus 15.2 ± 1.4, p = 0.004 au diagnostic et 18.0 ± 3.2 à T24). La longueur moyenne des télomères spermatiques ne variait pas entre les groupes. Après chimiothérapie, les patients présentaient la combinaison la plus élevée de télomères extrêmement courts et le nombre le plus élevé de télomères par tête de spermatozoïde (58% versus 29% après radiothérapie).Troisièmement, nous avons évalué les paramètres conventionnels et nucléaires (télomères et fragmentation de l'ADN) du sperme parmi une population de 50 donneurs de sperme fertiles et en bonne santé ayant donné des spermatozoïdes sur une période de 24 ans. Plus le don était ancien, plus la numération spermatique était élevée (r = 0.46, p = 001) et plus le nombre de signaux télomériques était faible (r = 0.27, p = 0.04). Les hommes plus âgés avaient une plus grande proportion de noyaux avec un nombre attendu de signaux (12-23). La distribution du nombre de télomères par tête spermatique différait entre les dons effectués avant 1998 et après 2000. Les hommes de moins de 36 ans ayant fait un don après 2000 avaient des télomères plus courts que les autres groupes.Nous avons montré que les altérations des télomères des spermatozoïdes sont présentes parallèlement aux altérations conventionnelles du spermogramme et au cancer des testicules. Nous nous soulevons des inquiétudes concernant la longueur des télomères spermatiques chez les jeunes hommes contemporains, parallèlement à la baisse mondiale du nombre de spermatozoïdes. Les télomères des spermatozoïdes apparaissent une cible précieuse pour l'évaluation de la qualité du sperme
Telomeres are pivotal structures of eukaryote biology, engaged in genome replication and protection. Their interactions with nuclear content are either direct or mediated via a shelterin complex named telosome. They are known to decreased after cell division. Sperm telomeres have specific roles and architecture. Organized in doublets and quadruplets, their number expected in a haploid sperm nucleus is comprised between 12 and 23. Essential but diminished during meiosis, they are subject to permanent restauration and lengthening in germinal sperm cells. Their length varies amongst individuals and generations, interrogating about factors implicated in sperm telomere shortening and disorganization. During the present work, we focused on three different situations. First, we investigate whether sperm telomere length and mean number of telomeres in sperm nucleus were related to oxidative stress and nuclear parameters alterations in a population of infertile males. We performed an prospective study over 52 males, with a case group of 30 infertile males presenting conventional semen parameter alterations and a control group of normozoospermic fertile males. Mean number of telomeres per sperm head was significantly elevated in infertile men with oligozoospermia (21.7 ± 4.3 versus 18.8 ± 3.0, p = 0.049) as were as intracytoplasmic reactive oxygen species and condensation defects. The higher number of telomeres, the more chromatin condensation defects were observed (r = 0.29, p 0.04). Secondly, we assessed the impact of testicular cancer and its therapy on sperm telomeres. We performed an ancillary study of 29 patients over a research project which had followed testicular cancer patients before and after adjuvant chemotherapy and radiotherapy. Patients had a higher number of telomere signal per sperm head than control before and after treatment (18.1 ± 2.7 versus 15.2 ± 1.4, p = 0.004 at diagnosis and 18.0 ± 3.2 at T24). Mean sperm telomere length did not vary between groups. Patients who received chemotherapy had the highest combination of extremely shorts sperm telomeres and highest number of telomeres per sperm head (58% versus 29% in the radiotherapy group). Thirdly, we assessed conventional and nuclear (telomeres and DNA fragmentation) semen parameters among a population of 50 healthy fertile sperm donor who donated spermatozoa over 24 years long timeframe. The older donation was, the higher sperm count (r = 0.46, p = 001). Older donations had less telomere signals (r = 0.27, p = 0.04). Older men had less alterations of telomere interactions and presented more sperm nucleus exhibiting the expected number of telomere signals (12-23). Distribution of telomere number per sperm head differed between donations made before 1998 and after 2000. Men under 36 who donated after 2000 had shorter telomeres than the other groups. We showed that sperm telomere alterations are presents alongside conventional semen alterations and testicular cancer. We raised concern regarding sperm telomere length of contemporary youth, in parallel to worldwide sperm count decline. Sperm telomeres are a valuable target for semen quality evaluation

In recent years, studies have demonstrated the shortening of sperm telomeres (STL) in infertile patients, which has been associated with decreased chromatin concentration and compaction, increased DNA fragmentation (sDNAfrag) and aneuploidy in sperm. However, there are studies that contradict these observations. The main purpose of this project was to clarify whether STL is related to sperm quality and its clinical outcomes. For that, we evaluated the STL of patients undergoing infertility treatments and analyzed its relationship with all the seminal parameters, chromatin maturity, sDNAfrag, aneuploidies and oxidative profile, as well as the clinical parameters after the treatments, using swim-up purified spermatozoa. No statistically significant differences were observed in relation to the seminal parameters in the population of purified spermatozoa, suggesting the importance of this method of selection for clinical use. Another original aspect was the observation that the population with the highest STL is reduced, but it has a higher rate of pregnancy (40%), and that the majority of the population is located in an STL range in which the rate of pregnancy is lower (29 %). In future studies we intend to increase the sample size to consolidate the obtained results and to complement them with additional methods.

Many studies suggest a direct relationship between toxic effects and an increase in the p53 protein on cellular DNA. For our studies, we used sperm DNA as an indicator of environmental toxic effects, dosing p53 quantitatively. To assess possible variations, we used semen samples from two homogeneous male groups living permanently in areas with different environmental impact. The toxic effects of the selected high environmental impact area are caused by both soil and air pollution, while the selected low environmental impact area is a nature reserve where there are no landfills, but only rural factories. As we work with reproductive cells, our interest was inevitably focused on sperm DNA damage and whether this damage could affect their fertilizing capacity. The length of telomeres and the quantification of protamines are being studied to better define the possible damage.