Effects of needle puncturing on re-vascularization and follicle survival in xenotransplanted human ovarian tissue
Tóm tắt
Ovarian tissue transplantation can restore fertility in young cancer survivors, however the detrimental loss of follicles following transplantation of cryopreserved ovarian tissue is hampering the efficiency of the procedure. This study investigates whether needle puncturing prior to transplantation can enhance revascularization and improve follicle survival in xenotransplanted human ovarian cortex. Cryopreserved human ovarian cortex pieces (N = 36) from 20 women aged 24–36 years were included. During the thawing process, each piece of tissue was cut in halves; one half serving as the untreated control and the other half was punctured approximately 150–200 times with a 29-gauge needle. The cortex pieces were transplanted subcutaneously to immunodeficient mice for 3, 6 and 10 days (N = 8 patients) and for 4 weeks (N = 12 patients). After 3, 6 and 10 days, revascularization of the ovarian xenografts were assessed using immunohistochemical detection of CD31 and gene expression of angiogenic factors (Vegfα, Angptl4, Ang1, and Ang2), and apoptotic factors (BCL2 and BAX) were performed by qPCR. Follicle density and morphology were evaluated in ovarian xenografts after 4 weeks. A significant increase in the CD31 positive area in human ovarian xenografts was evident from day 3 to 10, but no significant differences were observed between the needle and control group. The gene expression of Vegfα was consistently higher in the needle group compared to control at all three time points, but not statistically significant. The expression of Ang1 and Ang2 increased significantly from day 3 to day 10 in the control group (p < 0.001, p = 0.0023), however, in the needle group this increase was not observed from day 6 to 10 (Ang2 p = 0.027). The BAX/BCL2 ratio was similar in the needle and control groups. After 4-weeks xenografting, follicle density (follicles/mm3, mean ± SEM) was higher in the needle group (5.18 ± 2.24) compared to control (2.36 ± 0.67) (p = 0.208), and a significant lower percentage of necrotic follicles was found in the needle group (19%) compared to control (36%) (p = 0.045). Needle puncturing of human ovarian cortex prior to transplantation had no effect on revascularization of ovarian grafts after 3, 6 and 10 days xenotransplantation. However, needle puncturing did affect angiogenic genes and improved follicle morphology.
Tài liệu tham khảo
Yding Andersen C, Mamsen LS, Kristensen SG. FERTILITY PRESERVATION: freezing of ovarian tissue and clinical opportunities. Reproduction. 2019;158:F27-34. https://doi.org/10.1530/REP-18-0635.
Jensen AK, Macklon KT, Fedder J, Ernst E, Humaidan P, Andersen CY. 86 successful births and 9 ongoing pregnancies worldwide in women transplanted with frozen-thawed ovarian tissue: focus on birth and perinatal outcome in 40 of these children. J Assist Reprod Genet. 2017;34:325–36. https://doi.org/10.1007/S10815-016-0843-9.
Donnez J, Dolmans MM. Ovarian cortex transplantation: 60 reported live births brings the success and worldwide expansion of the technique towards routine clinical practice. J Assist Reprod Genet. 2015;32:1167–70. https://doi.org/10.1007/S10815-015-0544-9.
Mamsen LS, Kelsey TW, Ernst E, Macklon KT, Lund AM, Andersen CY. Cryopreservation of ovarian tissue may be considered in young girls with galactosemia. J Assist Reprod Genet. 2018;35:1209–17. https://doi.org/10.1007/S10815-018-1209-2.
Donnez PJ, Dolmans MM, Demylle D, Jadoul P, Pirard C, Squifflet J, et al. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet. 2004;364:1405–10. https://doi.org/10.1016/S0140-6736(04)17222-X.
Donnez J, Dolmans MM. Fertility preservation in women. N Engl J Med. 2017;377:1657–65. https://doi.org/10.1056/NEJMra1614676.
Donnez J, Dolmans MM, Diaz C, Pellicer A. Ovarian cortex transplantation: time to move on from experimental studies to open clinical application. Fertil Steril. 2015;104:1097–8. https://doi.org/10.1016/J.FERTNSTERT.2015.08.005.
Dolmans MM, Falcone T, Patrizio P. Importance of patient selection to analyze in vitro fertilization outcome with transplanted cryopreserved ovarian tissue. Fertil Steril. 2020;114:279–80. https://doi.org/10.1016/J.FERTNSTERT.2020.04.050.
Shapira M, Dolmans MM, Silber S, Meirow D. Evaluation of ovarian tissue transplantation: results from three clinical centers. Fertil Steril. 2020;114:388–97. https://doi.org/10.1016/J.FERTNSTERT.2020.03.037.
Jensen AK, Kristensen SG, Macklon KT, Jeppesen J V, Fedder J, Ernst E, et al. Outcomes of transplantations of cryopreserved ovarian tissue to 41 women in Denmark n.d. https://doi.org/10.1093/humrep/dev230.
Khattak H, Malhas R, Craciunas L, Afifi Y, Amorim CA, Fishel S, et al. Fresh and cryopreserved ovarian tissue transplantation for preserving reproductive and endocrine function: a systematic review and individual patient data meta-analysis. Hum Reprod Update. 2022;28:400–16. https://doi.org/10.1093/HUMUPD/DMAC003.
Gellert SE, Pors SE, Kristensen SG, Bay-Bjørn AM, Ernst E, Yding AC. Transplantation of frozen-thawed ovarian tissue: an update on worldwide activity published in peer-reviewed papers and on the Danish cohort. J Assist Reprod Genet. 2018;35:561–70. https://doi.org/10.1007/S10815-018-1144-2.
Janse F, Donnez J, Anckaert E, De Jong FH, Fauser BCJM, Dolmans MM. Limited value of ovarian function markers following orthotopic transplantation of ovarian tissue after gonadotoxic treatment. J Clin Endocrinol Metab. 2011;96:1136–44. https://doi.org/10.1210/JC.2010-2188.
Greve T, Schmidt KT, Kristensen SG, Ernst E, Andersen CY. Evaluation of the ovarian reserve in women transplanted with frozen and thawed ovarian cortical tissue. Fertil Steril. 2012;97:1394–8. https://doi.org/10.1016/J.FERTNSTERT.2012.02.036.
DueholmHjorth IM, Kristensen SG, Dueholm M, Humaidan P. Reproductive outcomes after in vitro fertilization treatment in a cohort of Danish women transplanted with cryopreserved ovarian tissue. Fertil Steril. 2020;114:379–87. https://doi.org/10.1016/J.FERTNSTERT.2020.03.035.
Lotz L, Dittrich R, Hoffmann I, Beckmann MW. Ovarian tissue transplantation: experience from Germany and worldwide efficacy. Clin Med Insights Reprod Heal. 2019;13:117955811986735. https://doi.org/10.1177/1179558119867357.
Dolmans MM, Martinez-Madrid B, Gadisseux E, Guiot Y, Yuan WY, Torre A, et al. Short-term transplantation of isolated human ovarian follicles and cortical tissue into nude mice. Reproduction. 2007;134:253–62. https://doi.org/10.1530/REP-07-0131.
Dath C, Van Eyck AS, Dolmans MM, Romeu L, DelleVigne L, Donnez J, et al. Xenotransplantation of human ovarian tissue to nude mice: comparison between four grafting sites. Hum Reprod. 2010;25:1734–43. https://doi.org/10.1093/HUMREP/DEQ131.
Gavish Z, Spector I, Peer G, Schlatt S, Wistuba J, Roness H, et al. Follicle activation is a significant and immediate cause of follicle loss after ovarian tissue transplantation. J Assist Reprod Genet. 2018;35:61–9. https://doi.org/10.1007/S10815-017-1079-Z.
Kristensen SG, Liu Q, Mamsen LS, Greve T, Pors SE, Bjørn AB, et al. A simple method to quantify follicle survival in cryopreserved human ovarian tissue. Hum Reprod. 2018;33:2276–84. https://doi.org/10.1093/HUMREP/DEY318.
Mamsen LS, Olesen HØ, Pors SE, Hu X, Bjerring P, Christiansen K, et al. Effects of Er:YAG laser treatment on re-vascularization and follicle survival in frozen/thawed human ovarian cortex transplanted to immunodeficient mice. J Assist Reprod Genet. 2021;38:2745–56. https://doi.org/10.1007/S10815-021-02292-0.
Gosden RG, Baird DT, Wade JC, Webb R. Restoration of fertility to oophorectomized sheep by ovarian autografts stored at -196 degrees C. Hum Reprod. 1994;9:597–603. https://doi.org/10.1093/OXFORDJOURNALS.HUMREP.A138556.
Baird DT, Campbell B, De Souza C, Telfer E. Long-term ovarian function in sheep after ovariectomy and autotransplantation of cryopreserved cortical strips. Eur J Obstet Gynecol Reprod Biol. 2004;113:55–9. https://doi.org/10.1016/j.ejogrb.2003.11.023.
Demeestere I, Simon P, Emiliani S, Delbaere A, Englert Y. Orthotopic and heterotopic ovarian tissue transplantation. Hum Reprod Update. 2009;15:649–65. https://doi.org/10.1093/HUMUPD/DMP021.
Mahmoodi M, Mehranjani MS, Mohammad S, Shariatzadeh A, Eimani H, Shahverdi A. N-acetylcysteine improves function and follicular survival in mice ovarian grafts through inhibition of oxidative stress. Reprod Biomed Online. 2015;30:101–10. https://doi.org/10.1016/j.rbmo.2014.09.013.
Olesen HØ, Pors SE, Jensen LB, Grønning AP, Lemser CE, Nguyen Heimbürger MTH, et al. N-acetylcysteine protects ovarian follicles from ischemia-reperfusion injury in xenotransplanted human ovarian tissue. Hum Reprod. 2021;36:429–43. https://doi.org/10.1093/humrep/deaa291.
Tuncer S, Atilgan R, Pala Ş, Kuloğlu T, Artaş G, Aydın S. N-Acetylcysteine and benfotiamine protect autotransplanted ovarian tissue from ischemia-reperfusion injury: an experimental Study. Exp Clin Transplant. 2018. https://doi.org/10.6002/ECT.2017.0320.
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;90:1550–8. https://doi.org/10.1016/J.FERTNSTERT.2007.08.086.
Manavella DD, Cacciottola L, Desmet CM, Jordan BF, Donnez J, Amorim CA, 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. Hum Reprod. 2018;33:270–9. https://doi.org/10.1093/humrep/dex374.
Gao J, Huang Y, Li M, Zhao H, Zhao Y, Li R, et al. Effect of local basic fibroblast growth factor and vascular endothelial growth factor on subcutaneously allotransplanted ovarian tissue in ovariectomized mice. PLoS One. 2015;10:e0134035. https://doi.org/10.1371/JOURNAL.PONE.0134035.
Kang BJ, Wang Y, Zhang L, Xiao Z, Li SW. bFGF and VEGF improve the quality of vitrified-thawed human ovarian tissues after xenotransplantation to SCID mice. J Assist Reprod Genet. 2016;33:281–9. https://doi.org/10.1007/S10815-015-0628-6.
Dolmans MM, Cacciottola L, Amorim CA, Manavella D. Translational research aiming to improve survival of ovarian tissue transplants using adipose tissue-derived stem cells. Acta Obstet Gynecol Scand. 2019;98:665–71. https://doi.org/10.1111/aogs.13610.
Cacciottola L, Nguyen TYT, Chiti MC, Camboni A, Amorim CA, Donnez J, et al. Long-term advantages of ovarian reserve maintenance and follicle development using adipose tissue-derived stem cells in ovarian tissue transplantation. J Clin Med. 2020;9:1–18. https://doi.org/10.3390/JCM9092980.
Cacciottola L, Courtoy GE, Nguyen TYT, Hossay C, Donnez J, Dolmans MM. Adipose tissue–derived stem cells protect the primordial follicle pool from both direct follicle death and abnormal activation after ovarian tissue transplantation. J Assist Reprod Genet. 2021;38:151–61. https://doi.org/10.1007/s10815-020-02005-z.
Allen KB, Mahoney A, Aggarwal S, Davis JR, Thompson E, Pak AF, et al. Transmyocardial revascularization (TMR): current status and future directions. Indian J Thorac Cardiovasc Surg. 2018;34:330–9. https://doi.org/10.1007/S12055-018-0702-7.
Hughes GC, Lowe JE, Kypson AP, St Louis JD, Pippen AM, Peters KG, et al. Neovascularization after transmyocardial laser revascularization in a model of chronic ischemia. Ann Thorac Surg. 1998;66:2029–36. https://doi.org/10.1016/S0003-4975(98)01095-9.
Malekan R, Reynolds C, Narula N, Kelley ST, Suzuki Y, Bridges CR. Angiogenesis in transmyocardial laser revascularization. A nonspecific response to injury. Circulation. 1998;98:II62-5 discussion II66.
Kohmoto T, DeRosa CM, Yamamoto N, Fisher PE, Failey P, Smith CR, et al. Evidence of vascular growth associated with laser treatment of normal canine myocardium. Ann Thorac Surg. 1998;65:1360–7. https://doi.org/10.1016/S0003-4975(98)00236-7.
Pelletier MP, Giaid A, Sivaraman S, Dorfman J, Li CM, Philip A, et al. Angiogenesis and growth factor expression in a model of transmyocardial revascularization. Ann Thorac Surg. 1998;66:12–8. https://doi.org/10.1016/S0003-4975(98)00388-9.
Yamamoto N, Kohmoto T, Gu A, DeRosa C, Smith CR, Burkhoff D. Angiogenesis is enhanced in ischemic canine myocardium by transmyocardial laser revascularization. J Am Coll Cardiol. 1998;31:1426–33. https://doi.org/10.1016/S0735-1097(98)00086-2.
Horvath KA, Chiu E, Maun DC, Lomasney JW, Greene R, Pearce WH, et al. Up-regulation of vascular endothelial growth factor mRNA and angiogenesis after transmyocardial laser revascularization. Ann Thorac Surg. 1999;68:825–9. https://doi.org/10.1016/S0003-4975(99)00842-5.
Mueller XM, Tevaearai HT, Von Segesser LK, Chaubert P, Genton CY. Does laser injury induce a different neovascularisation pattern from mechanical or ischaemic injuries? Heart. 2001;85:697–701. https://doi.org/10.1136/HEART.85.6.697.
Rosendahl M, Schmidt KT, Ernst E, Rasmussen PE, Loft A, Byskov AG, et al. Cryopreservation of ovarian tissue for a decade in Denmark: a view of the technique. Reprod Biomed Online. 2011;22:162–71. https://doi.org/10.1016/J.RBMO.2010.10.015.
Cadenas J, Pors SE, Nikiforov D, Zheng M, Subiran C, Bøtkjær JA, et al. Validating reference gene expression stability in human ovarian follicles, oocytes, cumulus cells, ovarian medulla, and ovarian cortex tissue. Int J Mol Sci. 2022;23:886. https://doi.org/10.3390/IJMS23020886.
Kristensen SG, Olesen H, Zeuthen MC, Pors SE, Andersen CY, Mamsen LS. Revascularization of human ovarian grafts is equally efficient from both sides of the cortex tissue. Reprod Biomed Online. 2022;44:991–4. https://doi.org/10.1016/J.RBMO.2022.02.009.
McLaughlin M, Innell HL, Anderson RA, Telfer EE. Inhibition of phosphatase and tensin homologue (PTEN) in human ovary in vitro results in increased activation of primordial follicles but compromises development of growing follicles. Mol Hum Reprod. 2014;20:736–44. https://doi.org/10.1093/MOLEHR/GAU037.
Gougeon A. Dynamics of follicular growth in the human: a model from preliminary results. Hum Reprod. 1986;1:81–7. https://doi.org/10.1093/oxfordjournals.humrep.a136365.
Xiao Z, Zhang Y, Fan W. Cryopreservation of human ovarian tissue using the silver closed vitrification system. J Assist Reprod Genet. 2017;34:1435–44. https://doi.org/10.1007/s10815-017-1004-5.
Cacciottola L, Manavella DD, Amorim CA, Donnez J, Dolmans MM. In vivo characterization of metabolic activity and oxidative stress in grafted human ovarian tissue using microdialysis. Fertil Steril. 2018;110:534-544.e3. https://doi.org/10.1016/j.fertnstert.2018.04.009.
Dissen GA, Lara HE, Fahrenbach WH, Costa ME, Ojeda SR. Immature rat ovaries become revascularized rapidly after autotransplantation and show a gonadotropin-dependent increase in angiogenic factor gene expression. Endocrinology. 1994;134:1146–54. https://doi.org/10.1210/ENDO.134.3.8119153.
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. https://doi.org/10.1530/JRF.0.1140341.
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. https://doi.org/10.1016/J.FERTNSTERT.2008.05.012.
Thurston G, Rudge JS, Ioffe E, Zhou H, Ross L, Croll SD, et al. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med. 2000;6:460–3. https://doi.org/10.1038/74725.
Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997;277:55–60. https://doi.org/10.1126/SCIENCE.277.5322.55.
Carmeliet P. Angiogenesis in health and disease. Nat Med. 2003;9:653–60. https://doi.org/10.1038/NM0603-653.
Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J. Vascular-specific growth factors and blood vessel formation. Nature. 2000;407:242–8. https://doi.org/10.1038/35025215.
Lobov IB, Brooks PC, Lang RA. Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. Proc Natl Acad Sci U S A. 2002;99:11205–10. https://doi.org/10.1073/PNAS.172161899.
Xu F, Stouffer RL. Local delivery of angiopoietin-2 into the preovulatory follicle terminates the menstrual cycle in rhesus monkeys. Biol Reprod. 2005;72:1352–8. https://doi.org/10.1095/BIOLREPROD.104.037143.
Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G, et al. Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med. 2006;12:235–9. https://doi.org/10.1038/NM1351.
Schuldt EA, Lieb W, Dörr M, Lerch MM, Völzke H, Nauck M, et al. Circulating angiopoietin-2 and its soluble receptor Tie-2 concentrations are related to inflammatory markers in the general population. Cytokine. 2018;105:1–7. https://doi.org/10.1016/J.CYTO.2018.02.003.
Geranmayeh MH, Rahbarghazi R, Farhoudi M. Targeting pericytes for neurovascular regeneration. Cell Commun Signal. 2019;17:26. https://doi.org/10.1186/S12964-019-0340-8.
Ito Y, Oike Y, Yasunaga K, Hamada K, Miyata K, Matsumoto S-I, et al. Inhibition of angiogenesis and vascular leakiness by angiopoietin-related protein 4. Cancer Res. 2003;63:6651–7.
Galaup A, Cazes A, Le Jan S, Philippe J, Connault E, Le Coz E, et al. Angiopoietin-like 4 prevents metastasis through inhibition of vascular permeability and tumor cell motility and invasiveness. Proc Natl Acad Sci U S A. 2006;103:18721–6. https://doi.org/10.1073/PNAS.0609025103.
Tan MJ, Teo Z, Sng MK, Zhu P, Tan NS. Emerging roles of angiopoietin-like 4 in human cancer. Mol Cancer Res. 2012;10:677–88. https://doi.org/10.1158/1541-7786.MCR-11-0519.
Le Jan S, Amy C, Cazes A, Monnot C, Lamandé N, Favier J, et al. Angiopoietin-like 4 is a proangiogenic factor produced during ischemia and in conventional renal cell carcinoma. Am J Pathol. 2003;162:1521–8. https://doi.org/10.1016/S0002-9440(10)64285-X.
Ng KTP, Xu A, Cheng Q, Guo DY, Lim ZXH, Sun CKW, et al. Clinical relevance and therapeutic potential of angiopoietin-like protein 4 in hepatocellular carcinoma. Mol Cancer. 2014;13:196. https://doi.org/10.1186/1476-4598-13-196.
De Roo C, Lierman S, Tilleman K, De Sutter P. In-vitro fragmentation of ovarian tissue activates primordial follicles through the Hippo pathway. Hum Reprod Open. 2020;2020:hoaa048. https://doi.org/10.1093/hropen/hoaa048.
Kawamura K, Cheng Y, Suzuki N, Deguchi M, Sato Y, Takae S, et al. Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci U S A. 2013;110:17474–9. https://doi.org/10.1073/PNAS.1312830110.
Lunding SA, Andersen AN, Hardardottir L, Olesen H, Kristensen SG, Andersen CY, et al. Hippo signaling, actin polymerization, and follicle activation in fragmented human ovarian cortex. Mol Reprod Dev. 2020;87:711–9. https://doi.org/10.1002/MRD.23353.
Atluri P, Panlilio CM, Liao GP, Suarez EE, McCormick RC, Hiesinger W, et al. Transmyocardial revascularization to enhance myocardial vasculogenesis and hemodynamic function. J Thorac Cardiovasc Surg. 2008;135:289–91. https://doi.org/10.1016/J.JTCVS.2007.09.043. 291.e1; discussion 291.