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Effects of age and oligosthenozoospermia on telomeres of sperm and blood cells

Published:October 24, 2021DOI:https://doi.org/10.1016/j.rbmo.2021.10.010

      Highlights

      • Sperm telomeres were shorter in older OAZ men than in older NZ men.
      • Younger OAZ men had a higher number of short telomeres in sperm and a tendency towards lower TERC accumulation.
      • Mean TL in PBMCs was shorter in younger OAZ patients, who also showed a higher percentage of short telomeres.
      • Positive correlations between STL and sperm count and motility were found in younger NZ men.
      • Sperm from younger NZ accumulated lower TRF1 mRNA levels.

      ABSTRACT

      Research question

      How do age and normo- or oligoasthenozoospermia affect telomere length (TL) dynamics in sperm and blood?

      Design

      Sperm and blood samples were collected from a cohort of 37 men aged 25 and under and 40 men aged 40 and over, with either normozoospermia (NZ) or oligoasthenozoospermia (OAZ). TL was evaluated using Q-FISH (quantitative fluorescence in situ hybridization). Telomerase mRNA (TERC and TERT) and shelterin (TRF1) gene expressions were analysed using quantitative real-time PCR (qRT-PCR). TRF1 protein levels were also evaluated using immunofluorescence (IF).

      Results

      Mean sperm telomere length (STL) increased with age in NZ group; older NZ men accumulated the longest telomeres. In blood samples, mean TL decreased with age in NZ groups. Interestingly, the younger OAZ group had the shortest mean TL and accumulated the highest percentage of short telomeres compared to the other groups. Analysis of TERC and TERT expression in sperm and blood did not show substantial differences among groups. Statistically significant positive correlations were found between STL and seminal parameters in younger NZ men. Protein levels of TRF1 in blood were similar in all groups analysed.

      Conclusions

      The OAZ group did not show the increase of STL with age that is normal in NZ individuals, suggesting that TL elongation mechanisms fail in OAZ patients. In blood, younger OAZ individuals showed short mean TL, suggesting that this parameter could be a good biomarker of OAZ in younger OAZ patients. Telomerase gene levels and TRF1 protein and mRNA levels did not differ between groups, therefore these factors cannot be used as OAZ biomarkers.

      KEYWORDS

      Abbreviation:

      ART (Assisted Reproductive Technology), GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase), IF (Immunofluorescence), NZ (Normozoospermic or Normozoospermia), OAZ (Oligoasthenozoospermic or Oligoasthenozoospermia), PBMCs (Peripheral Blood Mononuclear Cells), Q-FISH (Quantitative Fluorescence in Situ Hybridization), qRT-PCR (Quantitative Reverse Transcription Polymerase Chain Reaction), STL (Sperm Telomere Length), TA (Telomerase Activity), TERC (Telomerase RNA component), TERT (Telomerase Reverse Transcriptase), TIN2 (TRF1-interacting Nuclear Protein 2), TL (Telomere Length), TPP1 (TIN2- and POT1-interacting Protein 1), TRF1 (Telomeric Repeat-Binding Factor 1), TRF2 (Telomeric Repeat-Binding Factor 2), POT1 (Protection of Telomeres 1), RAP1 (Repressor Activator Protein 1)
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      Biography

      Carlos Balmori is Chief of the Urology and Andrology Department in IVIRMA Madrid. In 2019, he started his PhD in Telomere Research at the Rey Juan Carlos University and IVIRMA Madrid. His research interests focus on biomarkers of male fertility for diagnosis and treatment, as well as semen quality improvement techniques.
      Key message
      Telomere maintenance was altered in OAZ, leading to an impairment of STL elongation with age. Younger OAZ patients had shorter telomeres in blood. This opens the possibility of using PBMCs TL as a biomarker of OAZ.