Sperm and leukocyte telomere length are related to sperm quality parameters in healthy men from the Led-Fertyl study

Study question: Could sperm and leukocyte telomere length (TL) be associated with sperm quality parameters and reproductive health in men from the general population?

Summary answer: A positive association between sperm and leukocyte TL with sperm concentration and total count has been demonstrated.

What is known already: Male factors account for almost half of cases of couple infertility, and shorter TLs have been observed in sperm from men with impaired sperm parameters. However, evidence in men from the general population is limited.

Study design size duration: A total of 200 volunteers of reproductive age were recruited between February 2021 and April 2023 to participate in the Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters (Led-Fertyl) cross-sectional study.

Participants/materials setting methods: TLs in sperm and leukocytes were measured using quantitative polymerase chain reaction (qPCR) in 168 and 194 participants, respectively. Sperm parameters, including concentration, total count, motility, vitality, and morphology, were analyzed using a computer-assisted sperm analysis (CASA) SCA^® system according to the World Health Organization (WHO) 2010 guidelines. Multivariable regression models were performed to assess the associations between sperm and leukocyte TL, either in tertiles or as continuous variables, and sperm quality parameters while adjusting for potential confounders.

Main results and the role of chance: Participants in tertiles 2 (T2) and 3 (T3) of sperm TL showed a higher sperm concentration (β: 1.09; 95% CI: 0.09-2.09 and β: 2.06; 95% CI: 1.04-3.09 for T2 and T3, respectively; P-trend < 0.001), compared to those in the reference tertile (T1). Participants in the highest tertile of sperm TL showed higher total sperm count (β: 3.83; 95% CI: 2.08-5.58 for T3 vs T1; P-trend < 0.001). Participants in the top tertile of leukocyte TL showed higher sperm concentration (β: 1.49; 95% CI: 0.44-2.54 for T3 vs T1; P-trend = 0.004), and total count (β: 3.49; 95% CI: 1.62-5.35 for T3 vs T1; P-trend < 0.001) compared with participants in T1. These results remained consistent when sperm and leukocyte TL were modelled as continuous variables.

Limitations reasons for caution: One limitation is the impossibility of establishing a cause-effect relationship due to the cross-sectional study design. Additionally, the sample size of the study cannot be considered large.

Wider implications of the findings: Sperm and leukocyte TLs are associated with sperm quality parameters in the general population. Additional determinations and further studies with larger sample sizes are needed to clarify the mechanisms underlying these associations and to investigate the further implications.

Study funding/competing interests: The Led-Fertyl study was supported by the Spanish government's official funding agency for biomedical research, Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS) and co-funded by the European Union ERDF/ESF, 'A way to make Europe'/'Investing in your future' (PI21/01447), and the Diputació de Tarragona (2021/11-No.Exp. 8004330008-2021-0022642). J.S.-S., senior author of the present study, is partially supported by ICREA under the ICREA Academia program. M.F.d.l.P. was supported by a predoctoral grant from the Rovira i Virgili University and Diputació de Tarragona (2020-PMF-PIPF-8). C.V.-H. received a predoctoral grant from the Generalitat de Catalunya (2022 FI_B100108). M.Á.M. was supported by the Sara Borrell postdoctoral fellowship (CD21/00045-Instituto de Salud Carlos III (ISCIII)). All authors declare that they have no conflicts of interest.

Trial registration number: N/A.