Skip to main content
SpringerLink
Log in

Reduced sperm DNA longevity is associated with an increased incidence of still born; evidence from a multi-ovulating sequential artificial insemination animal model

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

Abstract

Purpose

Using a rabbit model, we assessed the influence of sperm DNA longevity on female reproductive outcomes.

Methods

Semen was collected from 40 bucks, incubated at 38 °C for 24 h, and the rate of sperm DNA fragmentation (rSDF) was determined using the sperm chromatin dispersion assay. Males were allocated into high rSDF (>0.5 units of increase per hour) or low rSDF (<0.5 units of increase per hour) groups. High and low rSDF semen samples were sequentially artificially inseminated into the same doe to reduce female factor variability, and pregnancy outcomes were recorded.

Results

While there was no difference in SDFs between rSDF groups immediately after collection (T0), differences were significant after 2 h of incubation; SDFs determined at collection and rSDF behaved as independent characters (Pearson correlation = 0.099; P = 0.542). Following artificial insemination, the rate of stillborn pups was significantly higher in does inseminated by males with a high rSDF (14/21) compared to those with low rSDF (15/6); (contingency χ2 5.19; p = 0.022). The risk of stillborn when low rSDF rabbits were used for insemination was 0.16, but increased to 0.36 when high rSDF animals were used (odds ratio = 2.85; 95 % confidence interval = 1.4–2.7).

Conclusion(s)

Dynamic assessment of SDF coupled with natural multiple ovulation, high fecundity of the rabbit and control over female factor influence, provided a useful experimental model to demonstrate the adverse effect of reduced sperm DNA longevity on reproductive outcome.

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
Fig. 2

Similar content being viewed by others

References

  1. Drobnis EZ, Johnson MH. Are we ready to incorporate sperm DNA-fragmentation testing into our male infertility work-up? A plea for more robust studies. Reprod Biomed Online. 2015;30:111–2.

  2. Palermo GD, Neri QV, Cozzubbo T, Rosenwaks Z. Perspectives on the assessment of human sperm chromatin integrity. Fertil Steril. 2014;102:1508–17.

    Article  CAS  PubMed  Google Scholar 

  3. Robinson L, Gallos ID, Conner SJ, Rajkhowa M, Miller D, Lewis S, et al. The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis. Hum Reprod. 2012;27:2908–17.

    Article  CAS  PubMed  Google Scholar 

  4. Zini A. Are sperm chromatin and DNA defects relevant in the clinic? Syst Biol Reprod Med. 2011;57:78–85.

    Article  PubMed  Google Scholar 

  5. Santiso R, Tamayo M, Gosálvez J, Johnston S, Mariño A, Fernández C, et al. DNA fragmentation dynamics allows the assessment of cryptic sperm damage in human: evaluation of exposure to ionizing radiation, hyperthermia, acidic pH and nitric oxide. Mutat Res. 2012;734:41–9.

    Article  CAS  PubMed  Google Scholar 

  6. Practice Committee of the American Society for Reproductive Medicine. The clinical utility of sperm DNA integrity testing: a guideline. Fertil Steril. 2013;99:673–7.

    Article  Google Scholar 

  7. Oliva R. Protamines and male infertility. Hum Reprod. 2006;12:417–35.

    Article  CAS  Google Scholar 

  8. Gosálvez J, López-Fernández C, Fernández JL, Gouraud A, Holt WV. Relationships between the dynamics of iatrogenic DNA damage and genomic design in mammalian sperm from eleven species. Mol Reprod Dev. 2011;78:951–61.

  9. Gosálvez J, Holt WV, Johnston SD. Sperm DNA fragmentation and its role in wildlife conservation. Reproductive sciences in animal conservation. Adv Exp Med Biol. 2014;753:357–84.

    Article  PubMed  Google Scholar 

  10. Gosálvez J, López-Fernández C, Arroyo F, Gosálbez A, Gutiérrez-Cortés El, Johnston SD. The assessment of sperm DNA damage in rabbits using the Halomax assay. In: Adamo G, Constanza A, editors. Rabbits: biology, diet and eating habits and disorders. New York: NOVA Science publishers; 2013. p. 87–100.

  11. Bencheik N. Effect de la fréquence de collecte de la semence sur les caractéristiques du sperme et des spermatozoides récoltés chez la lapin. Ann Zootech. 1995;44:263–79.

    Article  Google Scholar 

  12. Mocé E, Vicente JS, Lavara R. Effect of donor strain and maturation stage of rabbit oocytes on results of penetration test of rabbit semen. World Rabbit Sci. 2002;10:53–62.

    Google Scholar 

  13. Gosálvez J, López-Fernández C, Fernández JL, Esteves SC, Johnston SD. Unpacking the mysteries of sperm DNA fragmentation: ten frequently asked questions. J Reprod Biotech Fertil. 2015;4:1–16.

  14. Aurich C. Recent advances in cooled-semen technology. Anim Reprod Sci. 2008;107:268–75.

    Article  CAS  PubMed  Google Scholar 

  15. López-Fernández C, Gage MJ, Arroyo F, Gosálbez A, Larrán AM, Fernández JL, et al. Rapid rates of sperm DNA damage after activation in tench (Tinca tinca: Teleostei, Cyprinidae) measured using a sperm chromatin dispersion test. Reproduction. 2009;138:257–66.

    Article  PubMed  Google Scholar 

  16. Wdowiak A, Bojar I. Relationship between pregnancy, embryo development, and sperm deoxyribonucleic acid fragmentation dynamics. Saudi J Biol Sci. 2015 (in press). Published online ahead of print 10 August 2015. doi:10.1016/j.sjbs.2015.08.001.

  17. Zhao J, Zhang Q, Wang Y, Li Y. Whether sperm deoxyribonucleic acid fragmentation has an effect on pregnancy and miscarriage after in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis. Fertil Steril. 2014;102:998–1005.

    Article  CAS  PubMed  Google Scholar 

  18. Leach M, Aitken RJ, Sacks G. Sperm DNA fragmentation abnormalities in men from couples with a history of recurrent miscarriage. Aust NZ J Obst Gyn. 2015;55:379–83.

  19. Gosálvez J, Caballero P, López-Fernández C, Ortega L, Guijarro JA, Fernández JL, et al. Can DNA fragmentation of neat or swim-up spermatozoa be used to predict pregnancy following ICSI of fertile oocyte donors? Asian J Androl. 2013;15:812–8.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Genescà A, Caballín MR, Miró R, Benet J, Germà JR, Egozcue J. Repair of human sperm chromosome aberrations in the hamster egg. Hum Genet. 1992;89:181–6.

  21. Derijck A, van der Heijden G, Giele M, Philippens M, de Boer P. DNA double-strand break repair in parental chromatin of mouse zygotes, the first cell cycle as an origin of de novo mutation. Hum Mol Genet. 2008;17:1922–37.

  22. Marchetti F, Bishop J, Gingerich J, Wyrobek AJ. Meiotic interstrand DNA damage escapes paternal repair and causes chromosomal aberrations in the zygote by maternal misrepair. Sci Rep. 2015;5:7689.

  23. Gosálvez J, López-Fernández C, Hermoso A, Fernández JL, Kjelland ME. Sperm DNA fragmentation in zebrafish (Danio rerio) and its impact on fertility and embryo viability —Implications for fisheries and aquaculture. Aquaculture. 2014;433:173–82.

    Article  Google Scholar 

  24. Pérez-Cerezales S, Martínez-Páramo S, Beirão J, Herráez MP. Fertilization capacity with rainbow trout DNA-damaged sperm and embryo developmental success. Reproduction. 2010;139:989–97.

    Article  PubMed  Google Scholar 

  25. Devaux A, Fiat L, Gillet C, Bony S. Reproduction impairment following paternal genotoxin exposure in brown trout (Salmo trutta) and arctic charr (Salvelinus alpinus). Aquat Toxicol. 2011;101:405–11.

    Article  CAS  PubMed  Google Scholar 

  26. Fernández-Gonzalez R, Moreira PN, Pérez-Crespo M, Sánchez-Martín M, Ramırez MA, Pericuesta E, et al. Long-term effects of mouse intracytoplasmic sperm injection with DNA fragmented sperm on health and behavior of adult offspring. Biol Reprod. 2008;78:761–72.

  27. De Rycke M, Liebaers I, Van Steirteghem A. Epigenetic risks related to assisted reproductive technologies. Risk analysis and epigenetic inheritance. Hum Reprod. 2002;17:2487–94.

    Article  PubMed  Google Scholar 

  28. Kelly TL, Trasler JM. Reproductive epigenetics. Clin Genet. 2004;65:247–60.

    Article  CAS  PubMed  Google Scholar 

  29. Urrego R, Rodriguez-Osorio N, Niemann H. Epigenetic disorders and altered gene expression after use of assisted reproductive technologies in domestic cattle. Epigenetics. 2014;9:803–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This research was supported by the Spanish Ministry of Economy and Competitiveness, MINECO (BFU-2013-44290-R).

Author information

Authors and Affiliations

  1. School of Agriculture and Food Science, The University of Queensland, Gatton, Queensland, 4343, Australia

    Stephen D. Johnston

  2. Faculty of Biology, Autonomous University of Madrid, Cantoblanco, Madrid, Spain

    Carmen López-Fernández, Francisca Arroyo, Altea Gosálbez & Jaime Gosálvez

  3. Department of Genetics, Northeastern Biomedical Research Centre, The Mexican Social Security Institute, Monterrey, Mexico

    Elva I. Cortés Gutiérrez

  4. Unidad de Genética, Complejo Hospitalario Universitario A Coruña (CHUAC)-INIBIC and Centro Oncológico de Galicia, La Coruña, Spain

    Jose-Luis Fernández

Authors
  1. Stephen D. Johnston
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carmen López-Fernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francisca Arroyo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Altea Gosálbez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elva I. Cortés Gutiérrez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jose-Luis Fernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jaime Gosálvez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephen D. Johnston.

Additional information

Capsule

Sequential artificial insemination of the same naturally multi-ovulating female makes the rabbit a useful model for investigating the effect of sperm DNA longevity on reproductive outcome. Decreased sperm DNA longevity resulted in a diminished proportion of live offspring per pregnancy and an increased number of stillborn kittens.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Johnston, S.D., López-Fernández, C., Arroyo, F. et al. Reduced sperm DNA longevity is associated with an increased incidence of still born; evidence from a multi-ovulating sequential artificial insemination animal model. J Assist Reprod Genet 33, 1231–1238 (2016). https://doi.org/10.1007/s10815-016-0754-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-016-0754-9

Keywords

Search

Navigation