Telomere Length and Male Fertility

Abstract

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.

Sperm telomere length as a novel biomarker of male infertility and embryonic development: A systematic review and meta-analysis

“…However, some scholars have suggested that telomere length shortening may be a sign of sperm damage rather than a cause of sperm alteration ( 23 ). In contrast, some studies have concluded that STL is unrelated to sperm parameters ( 24 ).…”

Genetically Determined Telomere Length Is Associated with Pancreatic Neuroendocrine Neoplasms Onset

“…The estimate of the per-allele effect on TL (base pair increase/decrease according to each allele) for each SNP was obtained from the literature using GWAS data performed using leukocyte TL as outcome of interest [16]. Not all the genotyped individuals reached a call rate of 100%, and for this reason, and to be able to compute comparable score values for all study subjects, we also considered average values for the score (using the teloscore value divided by the number of genotyped SNPs) an approach that was successfully used in other studies [27, 28, 40]. Finally, the teloscore was transformed into quintiles based on its distribution in the controls.…”

“…TL is genetically determined, and 11 single nucleotide polymorphisms (SNPs) have shown a strong influence on this trait [16,[24][25][26]. A polygenic score generated with those 11 SNPs, called "teloscore" [15,27], has been successfully used in susceptibility studies of several human traits [28,29], including cancer [16,27,[30][31][32][33][34][35]. The advantage of using a genetic score is that it bypasses all the possible confounders, and it could give a more precise estimation of the causative association between TL and cancer risk.…”

Male Germ Cell Telomeres and Chemical Pollutants

“…On the one hand, studies in infertile men have shown that patients with short telomeres are unable or less likely to produce good-quality embryos compared to those with longer telomeres [23,33,38]. On the other hand, however, other authors have found no statistically significant differences in reproductive outcomes between spermatozoa with long and short telomeres and donor samples [39][40][41]. Although epidemiological retrospective studies can provide insight into general trends regarding the association between telomeres and infertility factors, they have limitations; these can include the sample size not always being sufficient to validate statistical results.…”