Abstract
Despite their important contribution to the cure of both oncological and benign diseases, gonadotoxic therapies present the risk of a severe impairment of fertility. Sperm cryopreservation is not an option to preserve prepubertal boys’ reproductive potential, as their seminiferous tubules only contain spermatogonial stem cells (as diploid precursors of spermatozoa). Cryobanking of human immature testicular tissue (ITT) prior to gonadotoxic therapies is an accepted practice. Evaluation of cryopreserved ITT using xenotransplantation in nude mice showed the survival of a limited proportion of spermatogonia and their ability to proliferate and initiate differentiation. However, complete spermatogenesis could not be achieved in the mouse model. Loss of germ cells after ITT grafting points to the need to optimize the transplantation technique. Tissue engineering, a new branch of science that aims at improving cellular environment using scaffolds and molecules administration, might be an approach for further progress. In this review, after summarizing the lessons learned from human prepubertal testicular germ cells or tissue xenotransplantation experiments, we will focus on the benefits that might be gathered using bioengineering techniques to enhance transplantation outcomes by optimizing early tissue graft revascularization, protecting cells from toxic insults linked to ischemic injury and exploring strategies to promote cellular differentiation.
Highlights
While oncological treatments can cure more than 80% of pediatric cancers in Europe [1], chemotherapeutic agents and radiotherapy have deleterious effects on the gonads of prepubertal boys [2,3]
Lessons Learned from Transplantation of Immature Testicular Tissue Fragments
With regard to transplantation of cryopreserved testicular tissue, grafting of human immature testicular tissue (ITT) has been so far exclusively performed in host nude mice [12,16,27,28,29,30,31]
Summary
While oncological treatments can cure more than 80% of pediatric cancers in Europe [1], chemotherapeutic agents and radiotherapy have deleterious effects on the gonads of prepubertal boys [2,3]. Loss of fertility significantly compromises quality of life [5], and surveys performed in cancer survivors have shown that 80% of these patients are considering parenthood, only 10% of them would use donor sperm or choose adoption [6,7]. Since intraTtehseticcuhloaircecobnettwameeinnadtiioffnerbeyntmoapltiigonnasnmt ucesltlsbewmasaddeesccornibsiedderiningaptphreodxiismeaasteeloyf2t1h%e poaftibeonyt.sSwinicthe ilneutrkaetmesitaic[u1l7a]racnodntxaemnointraatniosnplbayntmataiolingninanntucdeellms wicaesodf erasctrtiebsetidcuinlaarpcpelrlosxciomnatatemlyin2a1t%edobfybloeyuskewmitiha lceeullksebmrioau[g1h7t] atunmd oxrentroatrnasnmsipslsainotnatiinonthine nhuosdte[m18i]c,eaouftroa-ttrtaenstsipclualnatracteiollns coofnftraomzeinna-ttheadwbeydleguokneamdiaal ctieslslus ebrforauggmhtentutsmmoarytroannlsymbisescioonnsiindethreedhfoosrt f[e1r8ti]l,itayurtoes-ttroarnastipolnanptuartipoonseosf wfrhozenent-htheraewiesdnogornisakdoalf triestsruaensfmraigssmioenntosf mcaanyceorncleyllbsetocothnesicduerreeddpfaotriefnert.tiSliutychrerisstkormatuiostnaplsuorpboeseevsawluhateendtfhoerreotihsernoblroiosdk of retransmission of cancer cells to the cured patient. Such risk must be evaluated for other blood malignancies and for metastasizing cancers. In vitro maturation (IVM) of human prepubertal spermatogonia [20], which is currently under investigation, will be the only option; it will not be addressed in this review
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