Skip to main content

Advertisement

SpringerLink
Log in

Changes in the metabolic composition of storage solution with prolonged cold ischemia of the uterus

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

Abstract

Introduction

The development of uterine transplantation (UTx) from deceased donors requires knowledge of the tolerance of the uterus to prolonged cold ischemia (CI). This can be evaluated through the use of biological parameters to assess degradation of the organ between its procurement and transplantation. The objective of this study was to analyze changes in the metabolic composition of the storage solution in cases of prolonged CI in uteri from ewes.

Methods

Eighteen uterine auto-transplantations were performed in ewes. CI time was 1 h (T1) or 24 h (T24). Samples of Celsior® were taken when the explanted uterus was flushed (T0) and at the end of CI. A dual approach to metabolic analyses was followed: targeted biochemical analyses targeting several predefined metabolites and non-targeted metabolomics analyses based on nuclear magnetic resonance (NMR).

Results

Metabolic analyses were performed on 16 explanted uteri. Metabolomic profiles differed significantly between T1 and T24 (p = 0.003). Hypoxia-associated degradation of the organ was demonstrated by the significantly higher lactate levels at T24 than at T1 (p < 0.05), accompanied by cell lysis, and significantly higher levels of creatine kinase activity in T24 than in T1 uteri (p < 0.05). Oxidative stress increased over time, with a significantly higher oxidized glutathione/glutathione ratio for T24 than for T1 uteri (p < 0.05).

Conclusion

The metabolic results indicate a significant degradation of the uterus during 24 h of CI. Metabolic analysis of the storage solution could be used as a non-invasive tool for evaluating uterine degradation during CI before transplantation.

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
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Flyckt R, Kotlyar A, Arian S, Eghtesad B, Falcone T, Tzakis A. Deceased donor uterine transplantation. Fertil Steril. 2017;107:e13.

    Article  PubMed  Google Scholar 

  2. Kisu I, Kato Y, Obara H, Matsubara K, Matoba Y, Banno K, et al. Emerging problems in uterus transplantation. BJOG Int J Obstet Gynaecol. 2018;125:1352–6.

    Article  CAS  Google Scholar 

  3. Ejzenberg D, Andraus W, Baratelli Carelli Mendes LR, Ducatti L, Song A, Tanigawa R, et al. Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility. Lancet Lond Engl. 2019;392:2697–704.

    Article  Google Scholar 

  4. Kisu I, Mihara M, Banno K, Umene K, Araki J, Hara H, et al. Risks for donors in uterus transplantation. Reprod Sci Thousand Oaks Calif. 2013;20:1406–15.

    Article  Google Scholar 

  5. Lavoué V, Vigneau C, Duros S, Boudjema K, Levêque J, Piver P, et al. Which donor for uterus transplants: brain-dead donor or living donor? A systematic review. Transplantation. 2017;101:267–73.

    Article  PubMed  Google Scholar 

  6. Brännström M. Uterus transplantation and beyond. J Mater Sci Mater Med. 2017;28:70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bon D, Chatauret N, Giraud S, Thuillier R, Favreau F, Hauet T. New strategies to optimize kidney recovery and preservation in transplantation. Nat Rev Nephrol. 2012;8:339–47.

    Article  CAS  PubMed  Google Scholar 

  8. Favreau F, Giraud S, Bon D, Chatauret N, Thuillier R, Hauet T. Ischemia reperfusion control: the key of kidney graft outcomeMed Sci MS. 2013;29:183–8.

    Google Scholar 

  9. Fiehn O, Kopka J, Dörmann P, Altmann T, Trethewey RN, Willmitzer L. Metabolite profiling for plant functional genomics. Nat Biotechnol. 2000;18:1157–61.

    Article  CAS  PubMed  Google Scholar 

  10. Bonneau E, Tétreault N, Robitaille R, Boucher A, De Guire V. Metabolomics: perspectives on potential biomarkers in organ transplantation and immunosuppressant toxicity. Clin Biochem. 2016;49:377–84.

    Article  CAS  PubMed  Google Scholar 

  11. Barin-Le Guellec C, Largeau B, Bon D, Marquet P, Hauet T. Ischemia/reperfusion-associated tubular cells injury in renal transplantation: Can metabolomics inform about mechanisms and help identify new therapeutic targets? Pharmacol Res. 2018;129:34–43.

  12. Guy AJ, Nath J, Cobbold M, Ludwig C, Tennant DA, Inston NG, et al. Metabolomic analysis of perfusate during hypothermic machine perfusion of human cadaveric kidneys. Transplantation. 2015;99:754–9.

    Article  CAS  PubMed  Google Scholar 

  13. Bon D, Billault C, Claire B, Thuillier R, Hebrard W, Boildieu N, et al. Analysis of perfusates during hypothermic machine perfusion by NMR spectroscopy: a potential tool for predicting kidney graft outcome. Transplantation. 2014;97:810–6.

    Article  CAS  PubMed  Google Scholar 

  14. Dahm-Kähler P, Wranning C, Lundmark C, Enskog A, Mölne J, Marcickiewicz J, et al. Transplantation of the uterus in sheep: methodology and early reperfusion events. J Obstet Gynaecol Res. 2008;34:784–93.

    Article  PubMed  Google Scholar 

  15. Tricard J, Ponsonnard S, Tholance Y, Mesturoux L, Lachatre D, Couquet C, et al. Uterus tolerance to extended cold ischemic storage after auto-transplantation in ewes. Eur J Obstet Gynecol Reprod Biol. 2017;214:162–7.

    Article  PubMed  Google Scholar 

  16. Wranning CA, Marcickiewicz J, Enskog A, Dahm-Kähler P, Hanafy A, Brännström M. Fertility after autologous ovine uterine-tubal-ovarian transplantation by vascular anastomosis to the external iliac vessels. Hum Reprod Oxf Engl. 2010;25:1973–9.

    Article  CAS  Google Scholar 

  17. Ziegler F, Le Boucher J, Coudray-Lucas C, Cynober L. Plasma amino-acid determinations by reversed-phase HPLC: improvement of the orthophthalaldehyde method and comparison with ion exchange chromatography. J Autom Chem. 1992;14:145–9.

    Article  CAS  Google Scholar 

  18. Wei L, Xue T, Yang H, Zhao G-Y, Zhang G, Lu Z-H, et al. Modified uterine allotransplantation and immunosuppression procedure in the sheep model. PLoS One. 2013;8:e81300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wranning CA, Dahm-Kähler P, Mölne J, Nilsson UA, Enskog A, Brännström M. Transplantation of the uterus in the sheep: oxidative stress and reperfusion injury after short-time cold storage. Fertil Steril. 2008;90:817–26.

    Article  PubMed  Google Scholar 

  20. Karam G. Safety of the use of Celsior in kidney-pancreas transplantation. Progres En Urol J Assoc Francaise Urol Soc Francaise Urol. 2003;13:46–9.

    Google Scholar 

  21. Testa G, Koon EC, Johannesson L, McKenna GJ, Anthony T, Klintmalm GB, et al. Living donor uterus transplantation: a single center’s observations and lessons learned from early setbacks to technical success. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2017;17:2901–10.

    Article  CAS  Google Scholar 

  22. Brännström M, Johannesson L, Dahm-Kähler P, Enskog A, Mölne J, Kvarnström N, et al. First clinical uterus transplantation trial: a six-month report. Fertil Steril. 2014;101:1228–36.

    Article  PubMed  Google Scholar 

  23. Favreau F, Petit-Paris I, Hauet T, Dutheil D, Papet Y, Mauco G, et al. Cyclooxygenase 1-dependent production of F2-isoprostane and changes in redox status during warm renal ischemia-reperfusion. Free Radic Biol Med. 2004;36:1034–42.

    Article  CAS  PubMed  Google Scholar 

  24. Wranning CA, Mölne J, El-Akouri RR, Kurlberg G, Brännström M. Short-term ischaemic storage of human uterine myometrium--basic studies towards uterine transplantation. Hum Reprod Oxf Engl. 2005;20:2736–44.

    Article  Google Scholar 

  25. Faure JP, Petit I, Zhang K, Dutheil D, Doucet C, Favreau F, et al. Protective roles of polyethylene glycol and trimetazidine against cold ischemia and reperfusion injuries of pig kidney graft. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2004;4:495–504.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. INSERM, Inserm Unit U1248, 87000, Limoges, France

    Antoine Tardieu, P. Marquet, C. Barin-Le Guellec & T. Gauthier

  2. Department of Gynecologic and Obstetric, Hospital of Limoges, 87000, Limoges, France

    Antoine Tardieu, C. Sallée, F. Margueritte & T. Gauthier

  3. Faculty of Medicine, EA 6309 “Maintenance Myélinique et Neuropathies Périphériques”, University of Limoges, 87000, Limoges, France

    P. Chazelas, P-A. Faye & F. Favreau

  4. Laboratory of Biochemistry and Molecular genetics, Hospital of Limoges, 87000, Limoges, France

    P. Chazelas, P-A. Faye & F. Favreau

  5. Faculty of Medicine, University of Tours, 37000, Tours, France

    L. Nadal-Desbarats & C. Barin-Le Guellec

  6. Platform of Medicine, Imagery and experimental surgery (MICE), Hospital of Limoges, 87000, Limoges, France

    C-Y. Couquet

Authors
  1. Antoine Tardieu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Chazelas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P-A. Faye
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. Favreau
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L. Nadal-Desbarats
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C. Sallée
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F. Margueritte
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C-Y. Couquet
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. P. Marquet
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. C. Barin-Le Guellec
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. T. Gauthier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antoine Tardieu.

Ethics declarations

The research protocol was accepted by the regional ethics committee for animal experimentation in the Limousin region (CREEAL) (approval number 06-2014-06). Animal welfare was ensured in accordance with EU Directive 2010-63.

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

Tardieu, A., Chazelas, P., Faye, PA. et al. Changes in the metabolic composition of storage solution with prolonged cold ischemia of the uterus. J Assist Reprod Genet 36, 1169–1178 (2019). https://doi.org/10.1007/s10815-019-01477-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-019-01477-y

Keywords

Search

Navigation