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Sub-fertile sperm cells exemplify telomere dysfunction

  • Gamete Biology
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Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this study was to evaluate telomere homeostasis in sub-fertile compared to fertile human sperm.

Methods

This observational, comparative study included 16 sub-fertile men who required intracytoplasmic sperm injection and 10 fertile men. At least 100 sperm cells from each participant were assessed. Main outcome measures were telomere length and telomere aggregates. Telomerase RNA component (TERC) copy number and telomere capture were assessed using fluorescence in situ hybridization technique and human telomerase reverse transcriptase (hTERT) using immunohistochemistry.

Results

Clinical backgrounds were similar. The percentage of sperm cells with shorter telomeres was higher among the sub-fertile compared to the fertile participants (3.3 ± 3.1 vs. 0.6 ± 1.2%, respectively; P < 0.005). The percentage of cells with telomere aggregates was significantly higher in the sub-fertile group (15.12 ± 3.73 vs. 4.73 ± 3.73%; P < 0.005). TERC gene copy number was similar between groups. The percentage of cells that were positive for hTERT was lower in the sub-fertile group (3.81 ± 1.27 vs. 8.42 ± 1.80%; P < 0.005). Telomere capture rates were higher among the sub-fertile sperm cells (P < 0.005).

Conclusions

Sub-fertile sperm cells have short telomeres that are elongated by the alternative pathway of telomere capture. Dysfunctional telomeres may affect sperm fertilizability.

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References

  1. Desai N, Sabanegh E, Kim T, Agarwal A. Free radical theory of aging: implications in male infertility. Urology. 2010;75:14–9.

    Article  PubMed  Google Scholar 

  2. San Gabriel M, Zhang X, Zini A. Estimation of human sperm gene specific deoxyribonucleic acid damage by real time polymerase chain reaction analysis. Fertil Steril. 2006;85:797–9.

    Article  CAS  PubMed  Google Scholar 

  3. Huges CM, Lewis SE, McKelvey-Martin VJ, Thompson W. A comparison of baseline and induced DNA damage in human spermatozoa from fertile and infertile men, using a modified comet assay. Mol Hum Reprod. 1996;2:613–9.

    Article  Google Scholar 

  4. Zini A, Bielecki R, Phang D, Zenzes MT. Correlations between two markers of sperm DNA integrity, DNA denaturation and DNA fragmentation, in fertile and infertile men. Fertil Steril. 2001;75:674–7.

    Article  CAS  PubMed  Google Scholar 

  5. Zalenskaya IA, Zalensky AO. Telomeres in mammalian male germline cells. Int Rev Cytol. 2002;218:37–67.

    Article  CAS  PubMed  Google Scholar 

  6. Liu Y, Bohr VA, Lansdorp P. Telomere, telomerase and aging. Mech Ageing Dev. 2008;129:1–2.

    Article  PubMed  Google Scholar 

  7. Harley CB. Telomeres shorten during aging of human fibroblasts. Nature. 1990;345:458–60.

    Article  CAS  PubMed  Google Scholar 

  8. Biron-Shental T, Sukenik-Halevy R, Sharon Y, Goldberg-Bittman L, Kidron D, Fejgin MD, et al. Short telomeres may play a role in placental dysfunction in preeclampsia and intrauterine growth restriction. Am J Obstet Gynecol. 2010;202:381.e17.

    Article  Google Scholar 

  9. Hug N, Lingner J. Telomere length homeostasis. Chromosoma. 2006;115:413–25.

    Article  CAS  PubMed  Google Scholar 

  10. Greider CW, Blackburn EH. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell. 1985;43:405–13.

    Article  CAS  PubMed  Google Scholar 

  11. Baird DM, Britt-Compton B, Rowson J, Amso NN, Gregory L, Kipling D. Telomere instability in males germline. Hum Mol Genet. 2006;15:45–51.

    Article  CAS  PubMed  Google Scholar 

  12. Fujisawa M, Tanka H, Tatsumi N, Okada H, Arakawa S, Kamidono S. Telomeres activity in the testis of infertile patients with selected causes. Hum Rep. 1998;13:1476–9.

    Article  CAS  Google Scholar 

  13. Amiel A, Goldzak G, Gaber E, Yosef G, Fejgin MD, Yukla M, et al. Random aneuploidy and telomere capture in chronic lymphocytic leukemia and chronic myeloid leukemia patients. Cancer Genet Cytogenet. 2005;163:12–6.

    Article  CAS  PubMed  Google Scholar 

  14. Zuffardi O, Bonaglia M, Ciccone R, Giorda R. Inverted duplications deletions: underdiagnosed rearrangements? Clin Genet. 2009;75:505–13.

    Article  CAS  PubMed  Google Scholar 

  15. Laish I, Mannasse-Green B, Hadary R, Biron-Shental T, Konikoff FM, Amiel A, et al. Telomere dysfunction in nonalcoholic fatty liver disease and cryptogenic cirrhosis. Cytogenet Genome Res. 2016;150:93–9.

    Article  PubMed  Google Scholar 

  16. Biron-Shental T, Sadeh-Mestechkin D, Amiel A. Telomere homeostasis in IUGR placentas—a review. Placenta. 2016;39:21–3.

    Article  CAS  PubMed  Google Scholar 

  17. Bernadotte A, Mikhelson VM, Spivak IM. Markers of cellular senescence. Telomere shortening as a marker of cellular senescence. Aging (Albany NY). 2016;8:3–11.

    Article  Google Scholar 

  18. Cheng YY, Kao TW, Chang YW, Wu CJ, Peng TC, Wu LW, Yang HF, Liaw FY, Chen WL. Examining the gender difference in the association between metabolic syndrome and the mean leukocyte telomere length. PLoS One. 2017;12(7):e0180687. https://doi.org/10.1371/journal.pone.0180687.eCollection2017

  19. Révész D, Milaneschi Y, Verhoeven JE, Lin J, Penninx BW. Longitudinal associations between metabolic syndrome components and telomere shortening. J Clin Endocrinol Metab. 2015;100:3050–9.

    Article  PubMed  Google Scholar 

  20. Hanna CW, Bretherick KL, Gair JL, Fluker MR, Stephenson MD, Robinson WP. Telomere length and reproductive aging. Hum Rep. 2009;24:1206–11.

    Article  CAS  Google Scholar 

  21. Kinugawa C, Murakomi T, Okamura K, Yajima A. Telomerase activity in normal ovaries and premature ovarian failure. Tokahy J Exp Med. 2000;190:231–8.

    Article  CAS  Google Scholar 

  22. Thilagavathi J, Kumar M, Mishra SS, Venkatesh S, Kumar R, Dada R. Analysis of sperm telomere length in men with idiopathic infertility. Arch Gynecol Obstet. 2013;287:803–7.

    Article  CAS  PubMed  Google Scholar 

  23. Ferlin A, Rampazzo E, Rocca MS, Keppel S, Frigo AC, De Rossi A, et al. In young men sperm telomere length is related to sperm number and parental age. Hum Reprod. 2013;28:3370–6.

    Article  CAS  PubMed  Google Scholar 

  24. O'Sullivan JN, Finley JC, Risques RA, Shen WT, Gollahon KA, Moslovitz AH, et al. Telomere length assessment in tissue sections by quantitative FISH: image analysis algorithms. Cytometry. 2004;58:120–31.

    Article  PubMed  Google Scholar 

  25. Keefe DL, Liu L. Telomeres and reproductive aging. Reprod Fertil Dev. 2009;21:10–4.

    Article  CAS  PubMed  Google Scholar 

  26. Butts S, Riethman H, Ratcliffe S, Shaunik A, Coutifaris C, Barnhart K. Correlation of telomere length and telomerase activity with occult ovarian insufficiency. J Clin Endocrinol Metab. 2009;94:4835–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Shen H, Ong C. Detection of oxidative DNA damage in human sperm and its association with sperm function and male infertility. Free Radic Biol Med. 2000;28:529–36.

    Article  CAS  PubMed  Google Scholar 

  28. Rocca MS, Speltra E, Menegazzo M, Garolla A, Foresta C, Ferlin A. Sperm telomere length as a parameter of sperm quality in normozoospermic men. Hum Reprod. 2016;31:1158–63.

    Article  CAS  PubMed  Google Scholar 

  29. Aydos SE, Elhan AH, Tukun A. Is telomere length one of the determinants of reproductive life span? Arch Gynecol Obstet. 2005;272:113–6.

    Article  PubMed  Google Scholar 

  30. Hemann MT, Rudolph KL, Strong MA, DePinho RA, Chin L, Greider CW. Telomere dysfunction triggers developmentally regulated germ cell apoptosis. Mol Biol Cell. 2001;12:2023–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Fujisawa M, Tanaka H, Tatsumi N, Okada H, Arakawa S, Kamidono S. Telomerase activity in the testis of infertile patients with selected causes. Hum Reprod. 1998;13:1476–9.

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was not funded.

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Correspondence to Tal Biron-Shental.

Ethics declarations

The study was approved by the institutional Ethics Review Board. All patients provided signed informed consent.

Conflict of interest

The authors declare that they have no conflicts of interest.

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Biron-Shental, T., Wiser, A., Hershko-Klement, A. et al. Sub-fertile sperm cells exemplify telomere dysfunction. J Assist Reprod Genet 35, 143–148 (2018). https://doi.org/10.1007/s10815-017-1029-9

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  • DOI: https://doi.org/10.1007/s10815-017-1029-9

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