Abstract
Purpose
The aim of this research is to study whether basic fibroblast growth factor (bFGF) alone or in combination with vascular endothelial growth factor (VEGF) could improve the quality of vitrified-thawed human ovarian tissue xenotransplanted to severe combined immune deficiency (SCID) mice.
Methods
After collection and cryopreservation, thawed human ovarian tissue were cultured in vitro for 2 days and then xenografted to severe combined immune deficiency (SCID) mice for 7 days. The in vitro culture medium was separated into six groups, including (A) the blank control group, (B) the human recombinant bFGF (150 ng/ml) group, (C) the bFGF (150 ng/ml)+human recombinant VEGF (25 ng/ml) group, (D) bFGF (150 ng/ml)+VEGF (50 ng/ml) group, (E) bFGF (150 ng/ml)+ VEGF (75 ng/ml) group and (F) bFGF (150 ng/ml) + VEGF (100 ng/ml) group. In addition, eight pieces of thawed ovarian tissue were transplanted without in vitro culture, which serve as the fresh control group. The effect of transplantation was assessed by histological analysis, immunohistochemical staining for CD34, Ki-67, and AC-3 expression, and microvessel density (MVD).
Results
There was no significant difference between the fresh and blank control group. Compared to the blank control group, the number of follicles, MVD, and rate of Ki-67-positive cells increased significantly in groups B, C, D, E, and F, while apoptosis decreased significantly. Compared to the bFGF treatment group, no significant difference appeared in group C, D, E, and F.
Conclusions
The administration of bFGF alone or in combination with VEGF improved the quality of postgraft human ovarian tissue, though VEGF, regardless of different concentrations, did not influence effect of bFGF.
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References
Friedman O, Orvieto R, Fisch B, Felz C, Freud E, Ben-Haroush A, et al. Possible improvements in human ovarian grafting by various host and graft treatments. Hum Reprod. 2012;27:474–82.
Donnez J, Dolmans MM, Pellicer A, Diaz-Garcia C, Sanchez Serrano M, Schmidt KT, et al. Restoration of ovarian activity and pregnancy after transplantation of cryopreserved ovarian tissue: a review of 60 cases of reimplantation. Fertil Steril. 2013;99(6):1503–13.
Donnez J, Dolmans MM. Preservation of fertility in females with haematological malignancy. Br J Haematol. 2011;154:175–84.
Wang L, Ying YF, Ouyang YL, Wang JF, Xu J. VEGF and bFGF increase survival of xenografted human ovarian tissue in an experimental rabbit model. J Assist Reprod Genet. 2013;30(10):1301–11.
Grynberg M, Poulain M, Sebag-Peyrelevade S, le Parco S, Fanchin R, Frydman N. Ovarian tissue and follicle transplantation as an option for fertility preservation. Fertil Steril. 2012;97:1260–8.
Rosendahl M, Greve T, Andersen CY. The safety of transplanting cryopreserved ovarian tissue in cancer patients: a review of the literature. J Assist Reprod Genet. 2013;30(1):11–24.
Herraiz S, Novella-Maestre E, Rodríguez B, Díaz C, Sánchez-Serrano M, Mirabet V, et al. Improving ovarian tissue cryopreservation for oncologic patients: slow freezing versus vitrification, effect of different procedures and devices. Fertil Steril. 2014;101(3):775–84.
Keros V, Xella S, Hultenby K, Pettersson K, Sheikhi M, Volpe A, et al. Vitrification versus controlled-rate freezing in cryopreservation of human ovarian tissue. Hum Reprod. 2009;24(7):1670–83.
Wang Y, Xiao Z, Li L, Fan W, Li SW. Novel needle immersed vitrification: a practical and convenient method with potential advantages in mouse and human ovarian tissue cryopreservation. Hum Reprod. 2008;23:2256–65.
Liu J, Cheng KM, Silversides FG. Novel needle-in-straw vitrification can effectively preserve the follicle morphology, viability, and vascularization of ovarian tissue in Japanese quail (Coturnix japonica). Anim Reprod Sci. 2012;134(3–4):197–202.
Fatehi R, Ebrahimi B, Shahhosseini M, Farrokhi A, Fathi R. Effect of ovarian tissue vitrification method on mice preantral follicular development and gene expression. Theriogenology. 2014;81(2):302–8.
Xiao Z, Wang Y, Li LL, Li SW. In vitro culture thawed human ovarian tissue: NIV versus slow freezing method. Cryo Lett. 2013;34(5):520–6.
Xiao Z, Li SW, Zhang YY, Wang Y, Li LL, Fan W. NIV versus dropping vitrification in cryopreservation of human ovarian tissue. Cryo Lett. 2014;35(3):226–31.
Nugent D, Newton H, Gallivan L, Gosden RG. Protective effect of vitamin E on ischaemia-reperfusion injury in ovarian grafts. J Reprod Fertil. 1998;114:341–6.
Van Eyck AS, Jordan BF, Gallez B, Heilier JF, Van Langendonckt A, Donnez J. Electron paramagnetic resonance as a tool to evaluate human ovarian tissue reoxygenation after xenografting. Fertil Steril. 2009;92:374–81.
Demeestere I, Simon P, Emiliani S, Delbaere A, Englert Y. Orthotopic and heterotopic ovarian tissue transplantation. Hum Reprod Update. 2009;15:649–65.
Imthurn B, Cox SL, Jenkin G, Trounson AO, Shaw JM. Gonadotrophin administration can benefit ovarian tissue grafted to the body wall: implications for human ovarian grafting. Mol Cell Endocrinol. 2000;163:141–6.
Robinson RS, Woad KJ, Hammond AJ, Laird M, Hunter MG, Mann GE. Angiogenesis and vascular function in the ovary. Reproduction. 2009;138(6):869–81.
Kaczmarek MM, Schams D, Ziecik AJ. Role of vascular endothelial growth factor in ovarian physiology—an overview. Reprod Biol. 2005;5(2):111–36.
Araújo VR, Duarte AB, Bruno JB, Pinho Lopes CA, de Figueiredo JR. Importance of vascular endothelial growth factor (VEGF) in ovarian physiology of mammals. Zygote. 2013;21(3):295–304.
Gospodarowicz D, Cheng J, Lui GM, Baird A, Esch F, Bohlen P. Corpus luteum angiogenic factor is related to fibroblast growth factor. Endocrinology. 1985;117(6):2383–91.
Yamamoto S, Konishi I, Nanbu K, Komatsu T, Mandai M, Kuroda H, et al. Immunohistochemical localization of basic fibroblast growth factor (bFGF) during folliculogenesis in the human ovary. Gynecol Endocrinol. 1997;11(4):223–30.
Presta M, Dell’Era P, Mitola S, Moroni E, Ronca R, Rusnati M. Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev. 2005;16(2):159–78.
Murakami M, Simons M. Fibroblast growth factor regulation of neovascularization. Curr Opin Hematol. 2008;15(3):215–20.
Nilsson E, Parrott JA, Skinner MK. Basic fibroblast growth factor induces primordial follicle development and initiates folliculogenesis. Mol Cell Endocrinol. 2001;175:123–30.
Almeida AP, Saraiva MV, Alves Filho JG, Silva GM, Goncalves RF, Brito IR, et al. Gene expression and immunolocalization of fibroblast growth factor 2 in the ovary and its effect on the in vitro culture of caprine preantral ovarian follicles. Reprod Domest Anim. 2012;47:20–5.
Yun YR, Won JE, Jeon E, Lee S, Kang W, Jo H, et al. Fibroblast growth factors: biology, function, and application for tissue regeneration. J Tissue Eng. 2010;2010:218142.
Garor R, Abir R, Erman A, Felz C, Nitke S, Fisch B. Effects of basic fibroblast growth factor on in vitro development of human ovarian primordial follicles. Fertil Steril. 2009;91(5 Suppl):1967–75.
Peng X, Yang M, Wang L, Tong C, Guo Z. In vitro culture of sheep lamb ovarian cortical tissue in a sequential culture medium. J Assist Reprod Genet. 2010;27(5):247–57.
Gao JM, Yan J, Li R, Li M, Yan LY, Wang TR, et al. Improvement in the quality of heterotopic allotransplanted mouse ovarian tissues with basic fibroblast growth factor and fibrin hydrogel. Hum Reprod. 2013;28(10):2784–93.
Kedem A, Hourvitz A, Fisch B, Shachar M, Cohen S. Alginate scaffold for organ culture of cryopreserved-thawed human ovarian cortical follicles. J Assist Reprod Genet. 2011;28:761–9.
Chen SU, Chien CL, Wu MY, Chen TH, Lai SM, Lin CW, et al. Novel direct cover vitrification for cryopreservation of ovarian tissues increases follicle viability and pregnancy capability in mice. Hum Reprod. 2006;21(11):2794–800.
Kim SS. Assessment of long term endocrine function after transplantation of frozen-thawed human ovarian tissue to the heterotopic site: 10 year longitudinal follow-up study. J Assist Reprod Genet. 2012;29(6):489–93.
Dath C, Van Eyck AS, Dolmans MM, Romeu L, Delle Vigne L, Donnez J, et al. Xenotransplantation of human ovarian tissue to nude mice: comparison between four grafting sites. Hum Reprod. 2010;25(7):1734–43.
Liu J, Van der Elst J, Van den Broecke R, Dhont M. Early massive follicle loss and apoptosis in heterotopically grafted newborn mouse ovaries. Hum Reprod. 2002;17(3):605–11.
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):1368–79.
Dath C, Dethy A, Van Langendonckt A, Van Eyck AS, Amorim CA, Luyckx V, et al. Endothelial cells are essential for ovarian stromal tissue restructuring after xenotransplantation of isolated ovarian stromal cells. Hum Reprod. 2011;26(6):1431–9.
Kim SS, Soules MR, Battaglia DE. Follicular development, ovulation, and corpus luteum formation in cryopreserved human ovarian tissue after xenotransplantation. Fertil Steril. 2002;78(1):77–82.
Kim SS, Hwang IT, Lee HC. Heterotopic autotransplantation of cryobanked human ovarian tissue as a strategy to restore ovarian function. Fertil Steril. 2004;82(4):930–2.
Bedaiwy MA, Burlingame JM, Hussein M, Flyckt R, Assad R, Falcone T. Assessment of vascular endothelial growth factor, basic fibroblast growth factor, and transforming growth factor levels in amniotic fluid. J Reprod Med. 2012;57(9–10):405–10.
Tomao F, Papa A, Rossi L, Zaccarelli E, Caruso D, Zoratto F, et al. Angiogenesis and antiangiogenic agents in cervical cancer. Oncol Targets Ther. 2014;7:2237–48.
Ramchandani D, Weber GF. Interactions between osteopontin and vascular endothelial growth factor: implications for cancer. Biochim Biophys Acta. 2015;1855(2):202–22.
Lund EL, Thorsen C, Pedersen MW, Junker N, Kristjansen PE. Relationship between vessel density and expression of vascular endothelial growth factor and basic fibroblast growth factor in small cell lung cancer in vivo and in vitro. Clin Cancer Res. 2000;6:4287–91.
Otani N, Minami S, Yamoto M, Shikone T, Otani H, Nishiyama R, et al. The vascular endothelial growth factor/fms-like tyrosine kinase system in human ovary during the menstrual cycle and early pregnancy. J Clin Endocrinol Metab. 1999;84(10):3845–51.
Suzuki T, Sasano H, Takaya R, Fukaya T, Yajima A, Nagura H. Cyclic changes of vasculature and vascular phenotypes in normal human ovaries. Hum Reprod. 1998;13(4):953–9.
Fraser HM. Regulation of the ovarian follicular vasculature. Reprod Biol Endocrinol. 2006;4:18. doi:10.1186/1477-7827-4-18.
Hirschberg RM, Sachtleben M, Plendl J. Electron microscopy of cultured angiogenic endothelial cells. Microsc Res Tech. 2005;67(5):248–59.
Robinson RS, Hammond AJ, Mann GE, Hunter MG. A novel physiological culture system that mimics luteal angiogenesis. Reproduction. 2008;135(3):405–13.
Woad KJ, Hammond AJ, Hunter M, Mann GE, Hunter MG, Robinson RS. FGF2 is crucial for the development of bovine luteal endothelial networks in vitro. Reproduction. 2009;138:581–8.
Shirasuna K, Nitta A, Sineenard J, Shimizu T, Bollwein H, Miyamoto A. Vascular and immune regulation of corpus luteum development, maintenance, and regression in the cow. Domest Anim Endocrinol. 2012;43(2):198–211.
Wang TR, Yan LY, Yan J, Lu CL, Xia X, Yin TL, et al. Basic fibroblast growth factor promotes the development of human ovarian early follicles during growth in vitro. Hum Reprod. 2014;29(3):568–76.
Abir R, Fisch B, Jessel S, Felz C, Ben-Haroush A, Orvieto R. Improving posttransplantation survival of human ovarian tissue by treating the host and graft. Fertil Steril. 2011;95:1205–10.
Schubert B, Canis M, Darcha C, Artonne C, Pouly JL, Dechelotte P, et al. Human ovarian tissue from cortex surrounding benign cysts: a model to study ovarian tissue cryopreservation. Hum Reprod. 2005;20:1786–92.
Kitajima M, Defrère S, Dolmans MM, Colette S, Squifflet J, Van Langendonckt A, et al. Endometriomas as a possible cause of reduced ovarian reserve in women with endometriosis. Fertil Steril. 2011;96:685–91.
Soleimani R, Heytens E, Oktay K. Enhancement of neoangiogenesis and follicle survival by sphingosine-1-phosphate in human ovarian tissue xenotransplants. PLoS One. 2011;6, e19475.
Liu J, Van der Elst J, Van den Broecke R, Dhont M. Live offspring by in vitro fertilization of oocytes from cryopreserved primordial mouse follicles after sequential in vivo transplantation and in vitro maturation. Biol Reprod. 2001;64:171–8.
Acknowledgments
This work was supported by the National Natural Science Funds of China (31171442 to L. S. W and 31201117 to W. Y.).
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This research project had been approved by the Institutional Animal Care and Use Committee of Sichuan University (Sichuan, China).
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Human ovarian cortical tissue were collected from seven patients following informed consent and approval of the West China 2nd Hospital, West China Medical Center, Sichuan University Ethics committee.
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The administration of bFGF alone or in combination with VEGF improved the quality of postgraft human ovarian tissue, though VEGF, regardless of different concentrations, did not influence effect of bFGF.
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Kang, BJ., Wang, Y., Zhang, L. et al. bFGF and VEGF improve the quality of vitrified-thawed human ovarian tissues after xenotransplantation to SCID mice. J Assist Reprod Genet 33, 281–289 (2016). https://doi.org/10.1007/s10815-015-0628-6
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DOI: https://doi.org/10.1007/s10815-015-0628-6