Skip to main content

Advertisement

SpringerLink
Log in

Correlation of human telomerase reverse transcriptase single nucleotide polymorphisms with in vitro fertilisation outcomes

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To explore whether it is possible to predict the number and quality of the embryo using a few particular hTERT SNPs.

Methods

We included 997 Han Chinese women who were genetically unrelated and underwent assisted reproduction using IVF from September 2014 to December 2015. DNA was genotyped by using TaqMan real-time quantitative PCR.

Results

Among the 997 patients, individuals with the CC genotype of rs2075786 had a significantly lower number of good-quality embryos than those with the TT+TC genotypes. Compared with the CT+CC genotype carriers, patients carrying the TT genotype of rs2853677 had a significantly lower number of oocytes retrieved, mature oocytes and available embryos. Among the 750 patients aged ≤ 35 years, individuals with the AA+AG genotypes of rs2853691 had a significantly higher number of good-quality embryos than those with the GG genotype. The haplotype analysis showed that the TTTG (rs2853672/rs2853669/rs2735940/rs2736108) haplotype was more likely to lead to more than three good-quality embryos in patients aged ≤ 35 years.

Conclusions

Our study suggests that the hTERT SNP is associated with IVF outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Jirge PR. Poor ovarian reserve. J Hum Reprod Sci. 2016;9:63–9. https://doi.org/10.4103/0974-1208.183514.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Amer Coll Obstetricians; Practice Comm Amer Soc Reprod Med. Female age-related fertility decline. Fertil Steril. 2014;101(3):633–4. https://doi.org/10.1016/j.fertnstert.2013.12.032.

    Article  Google Scholar 

  3. Fang T, Su Z, Wang L, Yuan P, Li R, Ouyang N, et al. Predictive value of age-specific FSH levels for IVF-ET outcome in women with normal ovarian function. Reprod Biol Endocrinol. 2015;13:63. https://doi.org/10.1186/s12958-015-0056-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chronowska E. Regulation of telomerase activity in ovarian granulosa cells. Indian J Exp Biol. 2012;50:595–601.

    CAS  PubMed  Google Scholar 

  5. Townsley DM, Dumitriu B, Liu D, Biancotto A, Weinstein B, Chen C, et al. Danazol treatment for telomere diseases. N Engl J Med. 2016;374:1922–31. https://doi.org/10.1056/NEJMoa1515319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Schmidt JC, Cech TR. Human telomerase: biogenesis, trafficking, recruitment, and activation. Genes Dev. 2015;29:1095–105. https://doi.org/10.1101/gad.263863.115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wang W, Chen H, Li R, Ouyang N, Chen J, Huang L, et al. Telomerase activity is more significant for predicting the outcome of IVF treatment than telomere length in granulosa cells. Reproduction. 2014;147:649–57. https://doi.org/10.1530/REP-13-0223.

    Article  CAS  PubMed  Google Scholar 

  8. Chen H, Wang W, Mo Y, Ma Y, Ouyang N, Li R, et al. Women with high telomerase activity in luteinised granulosa cells have a higher pregnancy rate during in vitro fertilisation treatment. J Assist Reprod Genet. 2011;28:797–807. https://doi.org/10.1007/s10815-011-9600-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Greider CW, Blackburn EH. The telomere terminal transferase of Tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity. Cell. 1987;51:887–98. https://doi.org/10.1016/0092-8674(87)90576-9.

    Article  CAS  PubMed  Google Scholar 

  10. Liu JP, Li H. Telomerase in the ovary. Reproduction. 2010;140(2):215–22. https://doi.org/10.1530/REP-10-0008.

    Article  CAS  PubMed  Google Scholar 

  11. Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, et al. Extension of life-span by introduction of telomerase into normal human cells. Science. 1998;279:349–52. https://doi.org/10.1126/science.279.5349.349.

    Article  CAS  PubMed  Google Scholar 

  12. Lee J, Sung YH, Cheong C, Choi YS, Jeon HK, Sun W, et al. TERT promotes cellular and organismal survival independently of telomerase activity. Oncogene. 2008;27:3754–60. https://doi.org/10.1038/sj.onc.1211037.

    Article  CAS  PubMed  Google Scholar 

  13. Grossmann M. Danazol treatment for telomere diseases. N Engl J Med. 2016;375:1095–6. https://doi.org/10.1056/NEJMc1607752#SA1.

    Article  PubMed  Google Scholar 

  14. Melin BS, Nordfjall K, Andersson U, Roos G. hTERT cancer risk genotypes are associated with telomere length. Genet Epidemiol. 2012;36:368–72. https://doi.org/10.1002/gepi.21630.

    Article  PubMed  Google Scholar 

  15. Choi BJ, Yoon JH, Kim O, Choi WS, Nam SW, Lee JY, et al. Influence of the hTERT rs2736100 polymorphism on telomere length in gastric cancer. World J Gastroenterol. 2015;21:9328–36. https://doi.org/10.3748/wjg.v21.i31.9328.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zhang W, Chen Y, Yang X, Fan J, Mi X, Wang J, et al. Functional haplotypes of the hTERT gene, leukocyte telomere length shortening, and the risk of peripheral arterial disease. PLoS One. 2012;7:e47029. https://doi.org/10.1371/journal.pone.0047029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yan L, Wu S, Zhang S, Ji G, Gu A. Genetic variants in telomerase reverse transcriptase (TERT) and telomerase-associated protein 1 (TEP1) and the risk of male infertility. Gene. 2014;534:139–43. https://doi.org/10.1016/j.gene.2013.11.008.

    Article  CAS  PubMed  Google Scholar 

  18. Whitaker L, Critchley HO. Abnormal uterine bleeding. Best Pract Res Clin Obstet Gynaecol. 2016;34:54–65. https://doi.org/10.1016/j.bpobgyn.2015.11.012.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Balaban B, Brison D, Calderon G, Catt J, Conaghan J, Cowan L, et al. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26:1270–83. https://doi.org/10.1093/humrep/der037.

    Article  Google Scholar 

  20. Misiti S, Nanni S, Fontemaggi G, Cong YS, Wen J, Hirte HW, et al. Induction of hTERT expression and telomerase activity by estrogens in human ovary epithelium cells. Mol Cell Biol. 2000;20:3764–71. https://doi.org/10.1128/MCB.20.11.3764-3771.2000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lee HW, Blasco MA, Gottlieb GJ, Horner JW II, Greider CW, DePinho RA. Essential role of mouse telomerase in highly proliferative organs. Nature. 1998;392:569–74. https://doi.org/10.1038/33345.

    Article  CAS  PubMed  Google Scholar 

  22. Shay JW, Zou Y, Hiyama E, Wright WE. Telomerase and cancer. Hum Mol Genet. 2001;10:677–85. https://doi.org/10.1093/hmg/10.7.677.

    Article  CAS  PubMed  Google Scholar 

  23. Nakayama J, Tahara H, Tahara E, Saito M, Ito K, Nakamura H, et al. Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas. Nat Genet. 1998;18:65–8. https://doi.org/10.1038/ng0198-65.

    Article  CAS  PubMed  Google Scholar 

  24. Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, et al. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994;266:2011–5. https://doi.org/10.1126/science.7605428.

    Article  CAS  PubMed  Google Scholar 

  25. Wright WE, Piatyszek MA, Rainey WE, Byrd W, Shay JW. Telomerase activity in human germline and embryonic tissues and cells. Dev Genet. 1996;18:173–9. https://doi.org/10.1002/(SICI)1520-6408(1996)18:2<173::AID-DVG10>3.0.CO;2-3.

    Article  CAS  PubMed  Google Scholar 

  26. Ozturk S, Sozen B, Demir N. Telomere length and telomerase activity during oocyte maturation and early embryo development in mammalian species. Mol Hum Reprod. 2014;20(1):15–30. https://doi.org/10.1093/molehr/gat055.

    Article  CAS  PubMed  Google Scholar 

  27. Bellido F, Guinó E, Jagmohanchangur S, Seguí N, Pineda M, Navarro M, et al. Genetic variant in the telomerase gene modifies cancer risk in Lynch syndrome. Eur J Hum Genet. 2013;21(5):511–6. https://doi.org/10.1038/ejhg.2012.204.

    Article  CAS  PubMed  Google Scholar 

  28. Li X, Xu X, Fang J, Wang L, Mu Y, Zhang P, et al. Rs2853677 modulates Snail1 binding to the TERT enhancer and affects lung adenocarcinoma susceptibility[J]. Oncotarget. 2016;7(25):37825–38. https://doi.org/10.18632/oncotarget.9339.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank all of the research workers who contributed to this study. We thank Professor Yiming Wang, a senior geneticist, for the genetics advice and Professor Caixia Li, an advanced statistician, for the statistical support.

Funding

Merck Serono China Research Fund for Fertility Experts; Guangdong Medical Science and Technology Research Fund (Grant No. A2015143); Guangdong Provincial Natural Science Foundation (Grant No. 2015A030313086); Special Fund for Public Welfare Research and Capacity Building in Guangdong Province (social development areas) (Grant No. 2014A020213014). These funding sources provided financial support for the conduct of the research.

Author information

Author notes

  1. Hongmei Xu

    Present address: Department of Obstetrics and Gynaecology, Fuzhou General Hospital, Fuzhou, 350001, Fujian, People’s Republic of China

  2. Kailing Dai and Hongmei Xu contributed equally to this work.

Authors and Affiliations

  1. Reproductive Medicine Center, Department of Obstetrics and Gynaecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No.107, Yanjiang Xi Road, Guangzhou, 510120, Guangdong, People’s Republic of China

    Kailing Dai, Hongmei Xu, Nengyong Ouyang, Ying Li, Ping Yuan, Xiaomiao Zhao & Wenjun Wang

  2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, Guangdong, People’s Republic of China

    Kailing Dai, Hongmei Xu, Nengyong Ouyang, Xiaomiao Zhao & Wenjun Wang

  3. Department of Obstetrics and Gynaecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, Guangdong, People’s Republic of China

    Liangan Wang

Authors
  1. Kailing Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongmei Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nengyong Ouyang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ying Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ping Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Liangan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaomiao Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wenjun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed significantly to this work. Wenjun Wang designed the research study and wrote the paper; Kailing Dai, Hongmei Xu and Xiaomiao Zhao performed the experiments, analysed the data and wrote the manuscript; Nengyong Ouyang and Ping Yuan performed the experiments; Liangan Wang followed up the patients and collected the data; Ying Li collected the data and prepared figures and tables. All authors reviewed the manuscript. In addition, all authors approved the final draft.

Corresponding author

Correspondence to Wenjun Wang.

Ethics declarations

The project was approved by the reproductive ethics committee of the Sun Yat-Sen Memorial Hospital and has been registered in the Chinese Clinical Trial Registry under registration number ChiCTR-OCC-14005259.

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dai, K., Xu, H., Ouyang, N. et al. Correlation of human telomerase reverse transcriptase single nucleotide polymorphisms with in vitro fertilisation outcomes. J Assist Reprod Genet 36, 517–527 (2019). https://doi.org/10.1007/s10815-018-1379-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-018-1379-y

Keywords

Search

Navigation