Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2025-01-03T01:50:10.707Z Has data issue: false hasContentIssue false

Chapter 13 - Cryopreservation and Grafting of Immature Testicular Tissue

from Section 4 - Fertility Preservation Strategies in the Male

Published online by Cambridge University Press:  27 March 2021

By
Mina Mincheva  and
Stefan Schlatt
Edited by
Jacques Donnez  and
S. Samuel Kim
Jacques Donnez
Affiliation:
Catholic University of Louvain, Brussels
S. Samuel Kim
Affiliation:
University of Kansas School of Medicine
Get access

Summary

Over the past three decades survival rate in children and adolescents with cancer has doubled as a result of significant improvements in medical treatments [1]. Since more than 80% of children and adolescents diagnosed with cancer will survive ≥5 years beyond their diagnosis [2], one of the important concerns are the adverse effects of chemo- and radiotherapy on gonadal hormonal function and spermatogenesis [1]. Moreover, 80% of cancer survivors are intending to father their genetically own children, with only 10% acceptance of using donor sperm [3]. This scenario renders fertility preservation a pivotal aspect for the treatment of cancer in prepubertal boys and adolescents.

Spermatogonia are extremely susceptible to damage induced by chemo- or radiotherapy [4], and the extent of insult depends on the regimen and the cumulative dosage of treatments used [2]. Consequently, restoration of fertility following childhood cancer treatment will be dependent on the survival of sufficient numbers of spermatogonial stem cells (SSCs). In primates these can be recognized as the type Adark subtype which acts as regenerative reserve [4].

Type
Chapter
Information
Fertility Preservation
Principles and Practice
 , pp. 138 - 152
Publisher: Cambridge University Press
Print publication year: 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Robison, LL, Hudson, MM. Survivors of childhood and adolescent cancer: life-long risks and responsibilities. Nat Rev Cancer, 2014;14:61–70.Google Scholar
Picton, HM, Wyns, C, Anderson, RA et al. A European perspective on testicular tissue cryopreservation for fertility preservation in prepubertal and adolescent boys. Hum Reprod, 2015;30:2463–2475.Google Scholar
Vento, F Del, Vermeulen, M, Michele, F de et al. Tissue engineering to improve immature testicular tissue and cell transplantation outcomes: one step closer to fertility restoration for prepubertal boys exposed to gonadotoxic treatments. Int J Mol Sci, 2018;19:286.CrossRefGoogle ScholarPubMed
Jahnukainen, K, Ehmcke, J, Hou, M, Schlatt, S. Testicular function and fertility preservation in male cancer patients. Best Pract Res Clin Endocrinol Metab, 2011;25:287–302.Google Scholar
Alphen, MMA van, Kant HJG, van de, Rooij, DG de. Repopulation of the seminiferous epithelium of the rhesus monkey after X irradiation. Radiat Res, 1988;113:487–500.Google Scholar
Stukenborg, J-B, Jahnukainen, K, Hutka, M, Mitchell, RT. Cancer treatment in childhood and testicular function: the role of the somatic environment. Endocr Connect, 2018;EC-17–0382.Google Scholar
Skinner, R, Mulder, RL, Kremer, LC et al. Recommendations for gonadotoxicity surveillance in male childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consort. Lancet Oncol, 2017;18:e75–e90.Google Scholar
Heckmann, L, Langenstroth-Röwer, D, Pock, T et al. A diagnostic germ cell score for immature testicular tissue at risk of germ cell loss. Hum Reprod, 2018;33:636–645.CrossRefGoogle ScholarPubMed
Anderson, RA, Mitchell, RT, Kelsey, TW et al. Cancer treatment and gonadal function: experimental and established strategies for fertility preservation in children and young adults. Lancet Diabetes Endocrinol, 2015;3:556–567.CrossRefGoogle ScholarPubMed
Wallace, WHB, Anderson, RA, Irvine, DS. Fertility preservation for young patients with cancer: who is at risk and what can be offered? Lancet Oncol, 2005;6:209–218.Google Scholar
Keros, V, Hultenby, K, Borgström, B et al. Methods of cryopreservation of testicular tissue with viable spermatogonia in pre-pubertal boys undergoing gonadotoxic cancer treatment. Hum Reprod, 2007;22:1384–1395.Google Scholar
Stukenborg, J-B, Alves-Lopes, JP, Kurek, M et al. Spermatogonial quantity in human prepubertal testicular tissue collected for fertility preservation prior to potentially sterilizing therapy. Hum Reprod, 2018;33(9):1677–1683.CrossRefGoogle Scholar
Wyns, C, Langendonckt, A Van, Wese, FX, Donnez, J, Curaba, M. Long-term spermatogonial survival in cryopreserved and xenografted immature human testicular tissue. Hum Reprod, 2008;23:2402–2414.CrossRefGoogle ScholarPubMed
Baert, Y, Saen, D Van, Haentjens, P et al. What is the best cryopreservation protocol for human testicular tissue banking? Hum Reprod, 2013;28:1816–1826.Google Scholar
Wyns, C, Curaba, M, Martinez-Madrid, B et al. Spermatogonial survival after cryopreservation and short-term orthotopic immature human cryptorchid testicular tissue grafting to immunodeficient mice. Hum Reprod, 2007;22:1603–1611.Google Scholar
Wyns, C, Curaba, M, Petit, S et al. Management of fertility preservation in prepubertal patients: 5 years’ experience at the Catholic University of Louvain. Hum Reprod, 2011;26:737–747.Google Scholar
Saen, D Van, Vloeberghs, V, Gies, I et al. When does germ cell loss and fibrosis occur in patients with Klinefelter syndrome? Hum Reprod, 2018;33:1009–1022.Google Scholar
Jahnukainen, K, Mitchell, RT, Stukenborg, JB. Testicular function and fertility preservation after treatment for haematological cancer. Curr Opin Endocrinol Diabetes Obes, 2015;22:217–223.CrossRefGoogle ScholarPubMed
Masliukaite, I, Hagen, JM, Jahnukainen, K et al. Establishing reference values for age-related spermatogonial quantity in prepubertal human testes: a systematic review and meta-analysis. Fertil Steril, 2016;106:1652–1657.e2.Google Scholar
Poganitsch-Korhonen, M, Masliukaite, I, Nurmio, M et al. Decreased spermatogonial quantity in prepubertal boys with leukaemia treated with alkylating agents. Leukemia, 2017;31:1460–1463.Google Scholar
Tröndle, I, Westernströer, B, Wistuba, J et al. Irradiation affects germ and somatic cells in prepubertal monkey testis xenografts. Mol Hum Reprod, 2017;23:gax003.Google Scholar
Smart, E, Lopes, F, Rice, S et al. Chemotherapy drugs cyclophosphamide, cisplatin and doxorubicin induce germ cell loss in an in vitro model of the prepubertal testis. Sci Rep, 2018;8:1773.Google Scholar
Franik, S, Hoeijmakers, Y, D’Hauwers, K et al. Klinefelter syndrome and fertility: sperm preservation should not be offered to children with Klinefelter syndrome. Hum Reprod, 2016;31:1952–1959.Google Scholar
Onofre, J, Baert, Y, Faes, K, Goossens, E. Cryopreservation of testicular tissue or testicular cell suspensions: a pivotal step in fertility preservation. Hum Reprod Update, 2016;22:744–761.CrossRefGoogle ScholarPubMed
Uijldert, M, Meißner, A, Melker, AA de et al. Development of the testis in pre-pubertal boys with cancer after biopsy for fertility preservation. Hum Reprod, 2017;32:2366–2372.Google Scholar
Keros, V, Rosenlund, B, Hultenby, K et al. Optimizing cryopreservation of human testicular tissue: Comparison of protocols with glycerol, propanediol and dimethylsulphoxide as cryoprotectants. Hum Reprod, 2005;20:1676–1687.Google Scholar
Baert, Y, Braye, A, Struijk, RB, Pelt, AMM van,Goossens, E. Cryopreservation of testicular tissue before long-term testicular cell culture does not alter in vitro cell dynamics. Fertil Steril, 2015;104:1244–1252.e4.Google Scholar
Kvist, K, Thorup, J, Byskov, AG et al. Cryopreservation of intact testicular tissue from boys with cryptorchidism. Hum Reprod, 2006;21:484–491.CrossRefGoogle ScholarPubMed
Martinez, F. Update on fertility preservation from the Barcelona International Society for Fertility Preservation–ESHRE–ASRM 2015 expert meeting: indications, results and future perspectives. Hum Reprod, 2017;32:1802–1811.CrossRefGoogle ScholarPubMed
Oktay, K, Harvey, BE, Partridge, AH et al. Fertility preservation in patients with cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol, 2018;JCO.2018.78.191.Google Scholar
National Institute for Health and Care Excellence. Fertility problems: assessment and treatment. 2013; Available from: www.nice.org.uk/guidance/cg156/chapter/Recommendations#people-with-cancer-who-wish-to-preserve-fertilityGoogle Scholar
Liu, Z, Nie, YH, Zhang, CC et al. Generation of macaques with sperm derived from juvenile monkey testicular xenografts. Cell Res, 2016;26:139–142.Google Scholar
Honaramooz, A, Snedaker, A, Boiani, M et al. Sperm from neonatal mammalian testes grafted in mice. Nature, 2002;418:778–781.Google Scholar
Rathi, R, Zeng, W, Megee, S et al. Maturation of testicular tissue from infant monkeys after xenografting into mice. Endocrinology, 2008;149:5288–5296.Google Scholar
Honaramooz, A, Li, M-W, Penedo, MCT, Meyers, S, Dobrinski, I. Accelerated maturation of primate testis by xenografting into mice. Biol Reprod, 2004;70:1500–1503.Google Scholar
Jahnukainen, K, Ehmcke, J, Nurmio, M, Schlatt, S. Autologous ectopic grafting of cryopreserved testicular tissue preserves the fertility of prepubescent monkeys that receive sterilizing cytotoxic therapy. Cancer Res, 2012;72:5174–5178.Google Scholar
Wistuba, J, Luetjens, CM, Wesselmann, R et al. Meiosis in autologous ectopic transplants of immature testicular tissue grafted to callithrix jacchus. Biol Reprod, 2006;74:706–713.Google Scholar
Sato, Y, Taniguchi, M. Studying spermatogenesis by using In vivo and In vitro models: advantages and disadvantages of these models for practical use. J Vet Sci Technol, 2012;03:1–8.Google Scholar
Vermeulen, M, Poels, J, Michele, F de, Rieux, A des, Wyns, C. Restoring fertility with cryopreserved prepubertal testicular tissue: perspectives with hydrogel encapsulation, nanotechnology, and bioengineered scaffolds. Ann Biomed Eng, 2017;45:1770–1781.Google Scholar
Luetjens, MC, Stukenborg, J-B, Nieschlag, E, Simoni, M, Wistuba, J. Complete spermatogenesis in orthotopic but not in ectopic transplants of autologously grafted marmoset testicular tissue. Endocrinology, 2008;149:1736–1747.CrossRefGoogle Scholar
Saen, D Van, Goossens, E, Block, G De, Tournaye, H. Regeneration of spermatogenesis by grafting testicular tissue or injecting testicular cells into the testes of sterile mice: a comparative study.Fertil Steril, 2009;91:2264–2272.Google Scholar
Schlatt, S, Honaramooz, A, Ehmcke, J et al. Limited survival of adult human testicular tissue as ectopic xenograft. Hum Reprod, 2006;21:384–389.CrossRefGoogle ScholarPubMed
Goossens, E, Geens, M, Block, G De, Tournaye, H. Spermatogonial survival in long-term human prepubertal xenografts. Fertil Steril, 2008;90:2019–2022.CrossRefGoogle ScholarPubMed
Yu, J, Cai, Z-M, Wan, H-J et al. Development of neonatal mouse and fetal human testicular tissue as ectopic grafts in immunodeficient mice. Asian J Androl, 2006;8:393–403.Google Scholar
Mitchell, RT, Saunders, PTK, Childs, AJ et al. Xenografting of human fetal testis tissue: a new approach to study fetal testis development and germ cell differentiation. Hum Reprod, 2010;25:2405–2414.Google Scholar
Lo, KC, Yildiz, C, Zhu, Y et al. Human fetal testicular tissue xenotransplantation: a platform to study the effect of gonadotropins on human germ cell development in utero.J Urol, 2015;194:585–591.Google Scholar
Saen, D Van, Goossens, E, Haentjens, P, Baert, Y, Tournaye, H. Exogenous administration of recombinant human FSH does not improve germ cell survival in human prepubertal xenografts. Reprod Biomed Online, 2013;26:286–298.Google Scholar
Poels, J, Langendonckt, A Van, Many, MC, Wese, FX, Wyns, C. Vitrification preserves proliferation capacity in human spermatogonia. Hum Reprod, 2013;28:578–589.Google Scholar
Saen, D Van, Goossens, E, Bourgain, C, Ferster, A, Tournaye, H. Meiotic activity in orthotopic xenografts derived from human postpubertal testicular tissue. Hum Reprod, 2011;26:282–293.CrossRefGoogle ScholarPubMed
Poels, J, Abou-Ghannam, G, Herman, S et al. In search of better spermatogonial preservation by supplementation of cryopreserved human immature testicular tissue xenografts with N-acetylcysteine and testosterone. Front Surg, 2014;1:1–9.Google Scholar
Yokonishi, T, Sato, T, Katagiri, K et al. In vitro reconstruction of mouse seminiferous tubules supporting germ cell differentiation. Biol Reprod, 2013;89:1–6.Google Scholar
Mincheva, M, Sandhowe-Klaverkamp, R, Wistuba, J et al. Reassembly of adult human testicular cells: can testis cord-like structures be created in vitro? Mol Hum Reprod, 2018;24:55–63.Google Scholar
Gassei, K, Ehmcke, J, Wood, MA, Walker, WH, Schlatt, S. Immature rat seminiferous tubules reconstructed in vitro express markers of Sertoli cell maturation after xenografting into nude mouse hosts. Mol Hum Reprod, 2010;16:97–110.Google Scholar
Kita, K, Watanabe, T, Ohsaka, K et al. Production of functional spermatids from mouse germline stem cells in ectopically reconstituted seminiferous tubules. Biol Reprod, 2007;76:211–217.Google Scholar
Zhou, Q, Wang, M, Yuan, Y et al. Complete meiosis from embryonic stem cell-derived germ cells in vitro. Cell Stem Cell, 2016;18:330–340.Google Scholar
Ishikura, Y, Yabuta, Y, Ohta, H et al. In vitro derivation and propagation of spermatogonial stem cell activity from mouse pluripotent stem cells. Cell Rep, 2016;17:2789–2804.Google Scholar
Irie, N, Weinberger, L, Tang, WWC et al. SOX17 is a critical specifier of human primordial germ cell fate. Cell, 2015;160:253–268.Google Scholar
Park, TS, Galic, Z, Conway, AE et al. Derivation of primordial germ cells from human embryonic and induced pluripotent stem cells is significantly improved by coculture with human fetal gonadal cells.Stem Cells, 2009;27:783–795.Google Scholar
Vassena, R, Heindryckx, B, Peco, R et al. Genome engineering through CRISPR/Cas9 technology in the human germline and pluripotent stem cells. Hum Reprod Update, 2016;22:411–419.Google Scholar
Hutka M, Smith LB, Goossens E et al. Exogenous gonadotrophin stimulation induces partial maturation of human sertoli cells in a testicular xenotransplantation model for fertility preservation. J Clin Med, 2020;9:266.Google Scholar
Ntemou E, Kadam P, Van Saen D et al. Complete spermatogenesis in intratesticular testis tissue xenotransplants from immature non-human primate. Hum Reprod, 2019;34:403–413.Google Scholar
Goossens E, Jahnukainen K, Mitchell RT et al. Fertility preservation in boys: recent developments and new insights. Hum Reprod Open, 2020;3:hoaa016.Google Scholar
Braye A, Tournaye H, Goossens E. Setting up a cryopreservation programme for immature testicular tissue: lessons learned after more than 15 years of experience. Clin Med Insights Reprod Health, 2019;13:1179558119886342.Google Scholar
Fayomi AP, Peters K, Sukhwani M et al. Autologous grafting of cryopreserved prepubertal rhesus testis produces sperm and offspring. Science, 2019;363:1314–1319.Google Scholar
Mincheva M, Wistuba J, Brenker C et al. Challenging human somatic testicular cell reassembly by protein kinase inhibition-setting up a functional in vitro test system. Sci Rep, 2020;10:8935.CrossRefGoogle Scholar

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×