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Effect of Human Endothelial Progenitor Cell (EPC)- or Mouse Vascular Endothelial Growth Factor-Derived Vessel Formation on the Survival of Vitrified/Warmed Mouse Ovarian Grafts

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Abstract

The aim of this study was to evaluate the effectiveness of improving angiogenesis at graft sites on the survival of follicles in transplanted ovarian tissue. Matrigel containing 5 × 105 of cord blood-derived endothelial progenitor cells (EPCs) or 200 ng of mouse vascular endothelial growth factor (VEGF) was injected subcutaneously into BALB/c-Nu mice. After 1 week, vitrified/warmed ovaries from female B6D2F1 mice were subcutaneously transplanted into the injection sites. After 1, 2, and 4 weeks posttransplantation, the ovaries were recovered and subjected to histological analysis. Oocytes were collected from the transplanted ovaries, and their fertilization, embryonic development, and delivery were also observed. Vitrified/warmed ovaries transplanted into EPC- or VEGF-treated sites developed more blood vessels and showed better follicle survival than those transplanted into sham-injected sites. Normal embryonic development and consequent live births were obtained using oocytes recovered from cryopreserved/transplanted ovaries. Treatment with EPCs or VEGF could prevent the ischemic damage during the early revascularization stage of ovarian transplantation.

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References

  1. Wang X, Chen H, Yin H, Kim SS, Lin Tan S, Gosden RG. Fertility after intact ovary transplantation. Nature. 2002;415(6870): 385.

    Article  CAS  PubMed  Google Scholar 

  2. Donnez J, Dolmans MM, Demylle D, et al. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet. 2004;364(9443):1405–1410.

    Article  CAS  PubMed  Google Scholar 

  3. Meirow D, Levron J, Eldar Geva T, et al. Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy. N Engl J Med. 2005;353(3): 318–321.

    Article  CAS  PubMed  Google Scholar 

  4. Demeestere I, Simon P, Emiliani S, Delbaere A, Englert Y. Fertility preservation: successful transplantation of cryopreserved ovarian tissue in a young patient previously treated for Hodgkin’s disease. Oncologist. 2007;12(12):1437–1442.

    Article  PubMed  Google Scholar 

  5. Andersen CY, Rosendahl M, Byskov AG, et al. Two successful pregnancies following autotransplantation of frozen/thawed ovarian tissue. Hum Reprod. 2008;23(10):2266–2272.

    Article  PubMed  Google Scholar 

  6. Silber S, Kagawa N, Kuwayama M, Gosden R. Duration of fertility after fresh and frozen ovary transplantation. Fertil Steril. 2010;94(6):2191–2196.

    Article  PubMed  Google Scholar 

  7. Sanchez-Serrano M, Crespo J, Mirabet V, et al. Twins born after transplantation of ovarian cortical tissue and oocyte vitrification. Fertil Steril. 2010;93(1):268 e211–263.

    Article  Google Scholar 

  8. Donnez J, Squifflet J, Jadoul P, et al. Pregnancy and live birth after autotransplantation of frozen-thawed ovarian tissue in a patient with metastatic disease undergoing chemotherapy and hematopoietic stem cell transplantation. Fertil Steril. 2011; 95(5):1787 el781–1784.

    Article  Google Scholar 

  9. Demeestere I, Simon P, Moffa F, Delbaere A, Englert Y. Birth of a second healthy girl more than 3 years after cryopreserved ovarian graft. Hum Reprod. 2010;25(6):1590–1591.

    Article  CAS  PubMed  Google Scholar 

  10. Ernst E, Bergholdt S, Jorgensen JS, Andersen CY. The first woman to give birth to two children following transplantation of frozen/thawed ovarian tissue. Hum Reprod. 2010;25(5): 1280–1281.

    Article  PubMed  Google Scholar 

  11. Donnez J, Silber S, Andersen CY, et al. Children born after autotransplantation of cryopreserved ovarian tissue. a review of 13 live births. Ann Med. 2011;43(6):437–450.

    Article  PubMed  Google Scholar 

  12. Revel A, Laufer N, Ben Meir A, Lebovich M, Mitrani E. Micro-organ ovarian transplantation enables pregnancy: a case report. Hum Reprod. 2011;26(5):1097–1103.

    Article  PubMed  Google Scholar 

  13. Gook DA, Edgar DH, Stern C. Effect of cooling rate and dehydration regimen on the histological appearance of human ovarian cortex following cryopreservation in 1, 2-propanediol. Hum Reprod. 1999;14(8):2061–2068.

    Article  CAS  PubMed  Google Scholar 

  14. Gook DA, McCully BA, Edgar DH, McBain JC. Development of antral follicles in human cryopreserved ovarian tissue following xenografting. Hum Reprod. 2001;16(3):417–422.

    Article  CAS  PubMed  Google Scholar 

  15. Sztein JM, O’Brien MJ, Farley JS, Mobraaten LE, Eppig JJ. Rescue of oocytes from antral follicles of cryopreserved mouse ovaries: competence to undergo maturation, embryogenesis, and development to term. Hum Reprod. 2000;15(3):567–571.

    Article  CAS  PubMed  Google Scholar 

  16. Anasti JN, Kalantaridou SN, Kimzey LM, George M, Nelson LM. Human follicle fluid vascular endothelial growth factor concentrations are correlated with luteinizaton in spontanuously developing follicles. Hum Reprod. 1998;13(5):1144–1147.

    Article  CAS  PubMed  Google Scholar 

  17. Fraser HM, Lunn SF. Angiogenesis and its control in the female reproductive system. Br Med Bull. 2000;56(3):787–797.

    Article  CAS  PubMed  Google Scholar 

  18. Yamamoto S, Konishi I, Tsuruta Y, et al. Expression of vascular endothelial growth factor (VEGF) during folliculogenesis and corpus luteum formation in the human ovary. Gynecol Endocrinol. 1997;11(6):371–381.

    Article  CAS  PubMed  Google Scholar 

  19. Mattioli M, Barboni B, Turriani M, et al. Follicle activation involves vascular endothelial growth factor production and increased blood vessel extension. Biol Reprod. 2001;65(4): 1014–1019.

    Article  CAS  PubMed  Google Scholar 

  20. Hazzard TM, Xu F, Stouffer RL. Injection of soluble vascular endothelial growth factor receptor 1 into the preovulatory follicle disrupts ovulation and subsequent luteal function in rhesus monkeys. Biol Reprod. 2002;67(4):1305–1312.

    Article  CAS  PubMed  Google Scholar 

  21. Shimizu T, Iijima K, Ogawa Y, Miyazaki H, Sasada H, Sato E. Gene injections of vascular endothelial growth factor and growth differentiation factor-9 stimulate ovarian follicular development in immature female rats. Fertil Steril. 2008;89(5 suppl): 1563–1570.

    Article  CAS  PubMed  Google Scholar 

  22. Greenaway J, Connor K, Pedersen HG, Coomber BL, LaMarre J, Petrik J. Vascular endothelial growth factor and its receptor, Flk-1/KDR, are cytoprotective in the extravascular compartment of the ovarian follicle. Endocrinology. 2004;145(6):2896–2905.

    Article  CAS  PubMed  Google Scholar 

  23. Kezele PR, Ague JM, Nilsson E, Skinner MK. Alterations in the ovarian transcriptome during primordial follicle assembly and development. Biol Reprod. 2005;72(1):241–255.

    Article  CAS  PubMed  Google Scholar 

  24. Shikanov A, Zhang Z, Xu M, et al. Fibrin encapsulation and vascular endothelial growth factor delivery promotes ovarian graft survival in mice. Tissue Eng Part A. 2011;17(23–24):3095–3104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Danforth DR, Arbogast LK, Ghosh S, Dickerman A, Rofagha R, Friedman CI. Vascular endothelial growth factor stimulates pre-antral follicle growth in the rat ovary. Biol Reprod. 2003;68(5): 1736–1741.

    Article  CAS  PubMed  Google Scholar 

  26. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997; 275(5302):964–967.

    Article  CAS  PubMed  Google Scholar 

  27. Botta R, Gao E, Stassi G, et al. Heart infarct in NOD-SCID mice: therapeutic vasculogenesis by transplantation of human CD34+ cells and low dose CD34+KDR+ cells. FASEB J. 2004;18(12): 1392–1394.

    Article  CAS  PubMed  Google Scholar 

  28. Madeddu P, Emanueli C, Pelosi E, et al. Transplantation of low dose CD34+KDR+ cells promotes vascular and muscular regeneration in ischemic limbs. FASEB J. 2004;18(14):1737–1739.

    Article  CAS  PubMed  Google Scholar 

  29. Lee DR, Yang YH, Eum JH, et al. Effect of using slush nitrogen (SN2) on development of microsurgically manipulated vitrified/ warmed mouse embryos. Hum Reprod. 2007;22(9):2509–2514.

    Article  PubMed  Google Scholar 

  30. Lee MJ, Kim J, Lee KI, Shin JM, Chae JI, Chung HM. Enhancement of wound healing by secretory factors of endothelial precursor cells derived from human embryonic stem cells. Cytotherapy. 2011;13(2):165–178.

    Article  CAS  PubMed  Google Scholar 

  31. Park SJ, Moon SH, Lee HJ, et al. A comparison of human cord blood- and embryonic stem cell-derived endothelial progenitor cells in the treatment of chronic wounds. Biomaterials. 2013; 34(4):995–1003.

    Article  CAS  PubMed  Google Scholar 

  32. Randall GW, Awadalla SG, Shivers CA. Isolation, in vitro maturation, and fertilization of germinal vesicle oocytes obtained from the intact murine ovary. J In Vitro Fert Embryo Transf. 1990;7(6):314–320.

    Article  CAS  PubMed  Google Scholar 

  33. Liu J, Van der Eist J, Van den Broecke R, Dhont M. Early massive follicle loss and apoptosis in heterotopically grafted newborn mouse ovaries. Hum Reprod. 2002;17(3):605–611.

    Article  PubMed  Google Scholar 

  34. Israely T, Dafni H, Granot D, Nevo N, Tsafriri A, Neeman M. Vascular remodeling and angiogenesis in ectopic ovarian transplants: a crucial role of pericytes and vascular smooth muscle cells in maintenance of ovarian grafts. Biol Reprod. 2003;68(6):2055–2064.

    Article  CAS  PubMed  Google Scholar 

  35. Jeremias E, Bedaiwy MA, Gunmluoglu R, Biscotti CV, Siemionow M, Falcone T. Heterotopic autotransplantation of the ovary with microvascular anastomosis: a novel surgical technique. Fertil Steril. 2002;77(6): 1278–1282.

    Article  PubMed  Google Scholar 

  36. Israely T, Nevo N, Harmelin A, Neeman M, Tsafriri A. Reducing ischaemic damage in rodent ovarian xenografts transplanted into granulation tissue. Hum Reprod. 2006;21(6):1368–1379.

    Article  PubMed  Google Scholar 

  37. Soleimani R, Heytens E, Van den Broecke R, et al. Xenotransplantation of cryopreserved human ovarian tissue into murine back muscle. Hum Reprod. 2010;25(6):1458–1470.

    Article  CAS  PubMed  Google Scholar 

  38. Soleimani R, Van der Elst J, Heytens E, et al. Back muscle as a promising site for ovarian tissue transplantation, an animal model. Hum Reprod. 2008;23(3):619–626.

    Article  CAS  PubMed  Google Scholar 

  39. Van Eyck AS, Bouzin C, Feron O, et al. Both host and graft vessels contribute to revascularization of xenografted human ovarian tissue in a murine model. Fertil Steril. 2010;93(5):1676–1685.

    Article  PubMed  Google Scholar 

  40. Phillips HS, Hains J, Leung DW, Ferrara N. Vascular endothelial growth factor is expressed in rat corpus luteum. Endocrinology. 1990;127(2):965–967.

    Article  CAS  PubMed  Google Scholar 

  41. Huang EJ, Manova K, Packer AI, Sanchez S, Bachvarova RF, Besmer P. The murine steel panda mutation affects kit ligand expression and growth of early ovarian follicles. Dev Biol. 1993;157(1):100–109.

    Article  CAS  PubMed  Google Scholar 

  42. Parrott JA, Skinner MK. Kit-ligand/stem cell factor induces primordial follicle development and initiates folliculogenesis. Endocrinology. 1999;140(9):4262–4271.

    Article  CAS  PubMed  Google Scholar 

  43. Cohen T, Nahari D, Cerem LW, Neufeld G, Levi BZ. Interleukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem. 1996;271(2):736–741.

    Article  CAS  PubMed  Google Scholar 

  44. Ravindranath N, Little Ihrig L, Phillips HS, Ferrara N, Zeleznik AJ. Vascular endothelial growth factor messenger ribonucleic acid expression in the primate ovary. Endocrinology. 1992; 131(1):254–260.

    Article  CAS  PubMed  Google Scholar 

  45. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989;246(4935): 1306–1309.

    Article  CAS  PubMed  Google Scholar 

  46. Keck PJ, Hauser SD, Krivi G, et al. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science. 1989; 246(4935):1309–1312.

    Article  CAS  PubMed  Google Scholar 

  47. Ferrara N, Houck K, Jakeman L, Leung DW. Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev. 1992;13(1):18–32.

    Article  CAS  PubMed  Google Scholar 

  48. Skaznik Wikiel ME, Sharma RK, Selesniemi K, Lee HJ, Tilly JL, Falcone T. Granulocyte colony-stimulating factor in conjunction with vascular endothelial growth factor maintains primordial follicle numbers in transplanted mouse ovaries. Fertil Steril. 2011; 95(4):1405–1409.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Quintana R, Kopcow L, Sueldo C, Marconi G, Rueda NG, Bara-nao RI. Direct injection of vascular endothelial growth factor into the ovary of mice promotes follicular development. Fertil Steril. 2004;82 suppl 3:1101–1105.

    Article  CAS  PubMed  Google Scholar 

  50. Yang H, Lee HH, Lee HC, Ko DS, Kim SS. Assessment of vascular endothelial growth factor expression and apoptosis in the ovarian graft: can exogenous gonadotropin promote angiogenesis after ovarian transplantation? Fertil Steril. 2008;90(4 suppl): 1550–1558.

    Article  CAS  PubMed  Google Scholar 

  51. Yi C, Pan Y, Zhen Y, et al. Enhancement of viability of fat grafts in nude mice by endothelial progenitor cells. Dermatol Surg. 2006;32(12):1437–1443.

    CAS  PubMed  Google Scholar 

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Correspondence to Hyung Min Chung PhD or Dong Ryul Lee PhD.

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Cha, S.K., Shin, D.H., Kim, B.Y. et al. Effect of Human Endothelial Progenitor Cell (EPC)- or Mouse Vascular Endothelial Growth Factor-Derived Vessel Formation on the Survival of Vitrified/Warmed Mouse Ovarian Grafts. Reprod. Sci. 21, 859–868 (2014). https://doi.org/10.1177/1933719113518983

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