Skip to main content

Advertisement

Log in

Hypothermic machine perfusion after static cold storage improves ovarian function in rat ovarian tissue transplantation

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

Abstract

Objective

This study was performed to investigate the effect of hypothermic machine perfusion (HMP) after cold storage (CS) on ovarian transplantation.

Methods

Rats aged 8–10 weeks were used as the donors and recipients for allotransplantation. Eighteen donor rats were divided into three groups: the fresh control (n = 6), cold storage (CS; n = 6), and hypothermic machine perfusion (HMP; n = 6) groups. The preservation solution contained Dulbecco’s modified Eagle’s medium/Ham’s F-12 (1:1, v/v), 10% fetal bovine serum, 10 μg/ml insulin, 10 μg/ml transferrin, and 50 mIU/ml follicle-stimulating hormone (FSH). The donor ovaries in the CS and HMP groups were excised and then respectively subjected to 4 h of CS and 2 h of CS combined with 2 h of HMP at 4 °C, and then transplanted beneath the recipient’s left renal capsule. At 7 days after transplantation, the ovaries were removed and blood samples were obtained for histological analysis, immunohistochemistry for CD31 and Ki67, and serum anti-Mullerian hormone (AMH) level estimation.

Results

The HMP group showed significant increases in serum AMH and CD31-positive areas when compared to these values in the CS group (P < 0.05). However, no differences were noted in the total number of follicles or the Ki67-positive areas among the three groups.

Conclusion

Hypothermic machine perfusion after static cold storage is more effective than static CS alone for the short-term preservation of whole ovaries during transport. Whole ovary transplantation with vascular pedicle is our future research direction.

The black rectangle in the figure shows the place where ligation and disconnection are required, the black dotted line shows the place where vascular forceps are used to clamp, and the black circle shows the place where the cannula is inserted

This diagram was made for reviewers to understand more intuitively how my hypothermia mechanical perfusion model was built. Organs obtained in this way can be used for subsequent perfusion and whole ovarian transplantation

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

Access this article

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. International Agency for Research on Cancer. 2019. https://www.iarc.fr. Accessed 15 Feb 2019.

  2. Siegel R, Ma J, Zou Z, Jemal A. Each Year TACS. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.

    Article  Google Scholar 

  3. Donnez J, Dolmans MM. Fertility preservation in women. N Engl J Med. 2017;377(17):1657–65.

    Article  Google Scholar 

  4. Silber SJ. Fresh ovarian tissue and whole ovary transplantation. Semin Reprod Med. 2009;27(6):479–85.

    Article  Google Scholar 

  5. Mason JB, Cargill SL, Griffey SM, Reader JR, Anderson GB, Carey JR. Transplantation of young ovaries restored cardioprotective influence in postreproductive-aged mice. Aging Cell. 2011;10(3):448–56.

    Article  CAS  Google Scholar 

  6. Mason JB, Terry BC, Merchant SS, Mason HM, Nazokkarmaher M. Manipulation of ovarian function significantly influenced trabecular and cortical bone volume, architecture and density in mice at death. PLoS One. 2015;10(12):e0145821.

    Article  CAS  Google Scholar 

  7. Peterson RL, Parkinson KC, Mason JB. Restoration of immune and renal function in aged females by re-establishment of active ovarian function. Reprod Fertil Dev. 2017;29(10):2052–9.

    Article  CAS  Google Scholar 

  8. Mason JB, Cargill SL, Anderson GB, Carey JR. Transplantation of young ovaries to old mice increased life span in transplant recipients. J Gerontol Ser A Biol Med Sci. 2009;64A(12):1207–11.

    Article  Google Scholar 

  9. Westerkamp AC, Karimian N, Matton APM, Mahboub P, van Rijn R, Wiersema-Buist J, et al. Oxygenated hypothermic machine perfusion after static cold storage improves hepatobiliary function of extended criteria donor livers. Transplantation. 2016;100(4):825–35.

    Article  CAS  Google Scholar 

  10. Bathini V, McGregor T, McAlister VC, et al. Renal perfusion pump vs cold storage for donation after cardiac death kidneys: a systematic review. J Urol. 2013;189(6):2214–20.

    Article  Google Scholar 

  11. Henry SD, Guarrera JV. Protective effects of hypothermic ex vivo perfusion on ischemia/reperfusion injury and transplant outcomes. Transplant Rev. 2012;26(2):163–75.

    Article  Google Scholar 

  12. Dutkowski P, Guarrera JV, de Jonge J, Martins PN, Porte RJ, Clavien PA. Evolving trends in machine perfusion for liver transplantation. Gastroenterology. 2019;156(6):1542–7.

    Article  Google Scholar 

  13. Karcz M, Cook HT, Sibbons P, Gray C, Dorling A, Papalois V. An ex-vivo model for hypothermic pulsatile perfusion of porcine pancreata: hemodynamic and morphologic characteristics. Exp Clin Transplant. 2010;8(1):55–60.

    PubMed  Google Scholar 

  14. Kamoshita K, Okamoto N, Nakajima M, Haino T, Sugimoto K, Okamoto A, et al. Investigation of in vitro parameters and fertility of mouse ovary after storage at an optimal temperature and duration for transportation. Hum Reprod. 2016;31(4):774–81.

    Article  CAS  Google Scholar 

  15. Lee J, Kim EJ, Kong HS, Youm HW, Lee JR, Suh CS, et al. A combination of simvastatin and methylprednisolone improves the quality of vitrified-warmed ovarian tissue after auto-transplantation. Hum Reprod. 2015;30(11):2627–38.

    Article  CAS  Google Scholar 

  16. Damous LL, Silva SMD, Carbonel AAF, et al. Progressive evaluation of apoptosis, proliferation, and angiogenesis in fresh rat ovarian autografts under remote ischemic preconditioning. Reprod Sci. 2016;23(6):803–11.

    Article  CAS  Google Scholar 

  17. Fu Z, Ye Q, Zhang Y, Zhong Z, Xiong Y, Wang Y, et al. Hypothermic machine perfusion reduced inflammatory reaction by downregulating the expression of matrix metalloproteinase 9 in a reperfusion model of donation after cardiac death. Artif Organs. 2016;40(6):E102–11.

    Article  CAS  Google Scholar 

  18. Liu Z, Zhong Z, Lan J, Li M, Wang W, Yang J, et al. Mechanisms of hypothermic machine perfusion to decrease donation after cardiac death graft inflammation: through the pathway of upregulating expression of KLF2 and inhibiting TGF-β signaling. Artif Organs. 2017;41(1):82–8.

    Article  CAS  Google Scholar 

  19. Zeng X, Wang S, Li S, Yang Y, Fang Z, Huang H, et al. Hypothermic oxygenated machine perfusion alleviates liver injury in donation after circulatory death through activating autophagy in mice. Artif Organs. 2019;43(12):E320–32.

    Article  CAS  Google Scholar 

  20. Henry L, Labied S, Fransolet M, et al. Isoform 165 of vascular endothelial growth factor in collagen matrix improves ovine cryopreserved ovarian tissue revascularisation after xenotransplantation in mice. Reprod Biol Endocrinol. 2015;13:12.

    Article  CAS  Google Scholar 

  21. Tavana S, Valojerdi MR, Azarnia M, Shahverdi A. Restoration of ovarian tissue function and estrous cycle in rat after autotransplantation using hyaluronic acid hydrogel scaffold containing VEGF and bFGF. Growth Factors. 2016;34(3–4):97–106.

    Article  CAS  Google Scholar 

  22. Silber S, Pineda J, Lenahan K, DeRosa M, Melnick J. Fresh and cryopreserved ovary transplantation and resting follicle recruitment. Reprod BioMed Online. 2015;30(6):643–50.

    Article  Google Scholar 

  23. Lee J, Kong HS, Kim EJ, Youm HW, Lee JR, Suh CS, et al. Ovarian injury during cryopreservation and transplantation in mice: a comparative study between cryoinjury and ischemic injury. Hum Reprod. 2016;31(8):1827–37.

    Article  CAS  Google Scholar 

  24. Amorim CA, David A, Dolmans MM, Camboni A, Donnez J, van Langendonckt A. Impact of freezing and thawing of human ovarian tissue on follicular growth after long-term xenotransplantation. J Assist Reprod Genet. 2011;28(12):1157–65.

    Article  Google Scholar 

  25. Chiti MC, Dolmans MM, Orellana R, et al. Influence of follicle stage on artificial ovary outcome using fibrin as a matrix. Hum Reprod. 2015:dev299.

  26. Dewailly D, Andersen CY, Balen A, Broekmans F, Dilaver N, Fanchin R, et al. The physiology and clinical utility of anti-Mullerian hormone in women. Hum Reprod Update. 2014;20(3):370–85.

    Article  Google Scholar 

  27. Li J, Mao Q, He J, et al. Human umbilical cord mesenchymal stem cells improve the reserve function of perimenopausal ovary via a paracrine mechanism. Stem Cell Res Ther. 2017;8(1).

  28. Detti L, Fletcher NM, Saed GM, Sweatman TW, Uhlmann RA, Pappo A, et al. Xenotransplantation of pre-pubertal ovarian cortex and prevention of follicle depletion with anti-Müllerian hormone (AMH). J Assist Reprod Genet. 2018;35(10):1831–41.

    Article  Google Scholar 

  29. Lee J, Lee JR, Youm HW, Suh CS, Kim SH. Effect of preoperative simvastatin treatment on transplantation of cryopreserved-warmed mouse ovarian tissue quality. Theriogenology. 2015;83(2):285–93.

    Article  CAS  Google Scholar 

  30. Onions VJ, Webb R, Pincott-Allen C, Picton HM, Campbell BK. The effects of whole ovarian perfusion and cryopreservation on endothelial cell-related gene expression in the ovarian medulla and pedicle. Mol Hum Reprod. 2013;19(4):205–15.

    Article  CAS  Google Scholar 

  31. Isenberg JS, Frazier WA, Roberts DD. Thrombospondin- is a secreted protein that modulates vascular cell behavior via several cell surface receptors. In vitro NCOT. Thrombospondin-1: a physiological regulator of nitric oxide signaling. Cell Mol Life Sci. 2008;65(5):728–42.

    Article  CAS  Google Scholar 

  32. Greenaway J, Gentry PA, Feige JJ, LaMarre J, Petrik JJ. Thrombospondin and vascular endothelial growth factor are cyclically expressed in an inverse pattern during bovine ovarian follicle development. Biol Reprod. 2005;72(5):1071–8.

    Article  CAS  Google Scholar 

  33. Ma W, Zheng X, Hei C, et al. Optimal FSH usage in revascularization of allotransplanted ovarian tissue in mice. J Ovarian Res. 2017;10(1).

  34. Manavella DD, Cacciottola L, Desmet CM, et al. Adipose tissue-derived stem cells in a fibrin implant enhance neovascularization in a peritoneal grafting site: a potential way to improve ovarian tissue transplantation. Human Reprod. 2018;33(2):270–9.

    Article  CAS  Google Scholar 

  35. Xu J, Long YS, Gozal D, Epstein PN, Intermittent Hypoxia IH. SAOI. Beta-cell death and proliferation after intermittent hypoxia: role of oxidative stress. Free Radic Biol Med. 2009;46(6):783–90.

    Article  CAS  Google Scholar 

  36. Onions VJ, Mitchell MRP, Campbell BK, Webb R. Ovarian tissue viability following whole ovine ovary cryopreservation: assessing the effects of sphingosine-1-phosphate inclusion. Hum Reprod. 2008;23(3):606–18.

    Article  CAS  Google Scholar 

  37. Dittrich R, Lotz L, Keck G, Hoffmann I, Mueller A, Beckmann MW, et al. Live birth after ovarian tissue autotransplantation following overnight transportation before cryopreservation. Fertil Steril. 2012;97(2):387–90.

    Article  Google Scholar 

  38. Gerritse R, Beerendonk CC, Westphal JR, et al. Glucose/lactate metabolism of cryopreserved intact bovine ovaries as a novel quantitative marker to assess tissue cryodamage. Reprod BioMed Online. 2011;23(6):755–64.

    Article  CAS  Google Scholar 

  39. Ding Y, Shao J, Li J, et al. Successful fertility following optimized perfusion and cryopreservation of whole ovary and allotransplantation in a premature ovarian insufficiency rat model. J Ovarian Res. 2018;11(1).

  40. Torre A, Ben Brahim F, Popowski T, Boudjenah R, Salle B, Lornage J. Factors related to unstained areas in whole ewe ovaries perfused with a metabolic marker. Hum Reprod. 2013;28(2):423–9.

    Article  CAS  Google Scholar 

  41. Celik S, Celikkan FT, Ozkavukcu S, Can A, Celik-Ozenci C. Expression of inhibitor proteins that control primordial follicle reserve decreases in cryopreserved ovaries after autotransplantation. J Assist Reprod Genet. 2018;35(4):615–26.

    Article  Google Scholar 

Download references

Funding

This study was supported by the Natural Science Foundation of China (81570079).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yanfeng Wang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict 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

Zhang, S., Yao, H., Liu, Y. et al. Hypothermic machine perfusion after static cold storage improves ovarian function in rat ovarian tissue transplantation. J Assist Reprod Genet 37, 1745–1753 (2020). https://doi.org/10.1007/s10815-020-01797-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-020-01797-4

Keywords

Navigation