Effect of telomere length and related gene polymorphism in signaling pathway on semen quality

This study investigates sperm telomere length (STL), gene polymorphisms in telomere-related pathway genes, and semen quality, were detected to evaluate their potential as a biomarkers of semen quality. Associationally, it explores between gene polymorphisms and STL, and semen quality. A total of 1,349 male volunteers from the Pu-yang Reproductive Medicine Center were selected as research subjects. Computer-aided sperm analysis analysis was employed to assess semen parameters. Real-time fluorescence quantitative PCR was utilized to measure STL, while polymerase chain reaction was used to detect gene polymorphisms. The correlation between STL, related gene polymorphisms, and semen parameters was subsequently analyzed. Among the 1,349 subjects, the proportions of semen volume, total sperm count, sperm concentration, progressive motility, and total sperm motility meeting the criteria exceeded 80%, whereas the proportion of normal morphology was only 32.46%. The results of the restricted cubic spline (RCS) analysis indicated that STL exhibtied a nonlinear relationship with sperm concentration (P < 0.001) and total sperm count (P = 0.007). After categorizing STL levels into quartiles, the risk of abnormalities in total sprem count (OR = 0.37[0.15,0.94], P = 0.037), sperm concentration (OR = 0.31[0.11,0.83], P = 0.020), progressive motility (OR = 0.27[0.12,0.61)], P = 0.002), and total vitality percentage (OR = 0.19[0.07,0.51], P = 0.001) was lower in the third quartile when compared to the first quartile. We explored the relationship between genetic variation in three key telomere pathway genes (POT1, TERF1, and TERT), STL, and semen parameters. STL levels were significantly higher in individuals carrying the POT1 rs1034794 mutant allele than in type individuals (β = 6.17, P = 0.005). We observed that the POT1 rs1034794 and rs10250202 variants were negatively correlated with total sperm count (β=-64.47), progressive motility (β1=-9.76; β2=-6.99), and total vitality percentage (β1=-11.80; β2=-7.04). The TERT rs2735940 variant was negatively correlated with Wobble (WOB) and Linearity (LIN). There is a non-linear relationship between STL and sperm concentration as well as total sperm count. STL may serve as potentially reliable biomarker of semen quality. Furthermore, single nucleotide polymorphisms (SNPs) in telomere-associated pathway genes (POT1, TERT) were significantly associated with sperm parameters and STL. This suggests a novel hypothesis thought polymorphisms in telomere pathway genes may indirectly regulate semen parameters by affecting STL.