Progress in translational reproductive science: testicular tissue transplantation and in vitro spermatogenesis

Abstract

Since the birth of the first child conceived via in vitro fertilization 40 years ago, fertility treatments and assisted reproductive technology have allowed many couples to reach their reproductive goals. As of yet, no fertility options are available for men who cannot produce functional sperm, but many experimental therapies have demonstrated promising results in animal models. Both autologous (stem cell transplantation, de novo morphogenesis, and testicular tissue grafting) and outside-the-body (xenografting and in vitro spermatogenesis) approaches exist for restoring sperm production in infertile animals with varying degrees of success. Once safety profiles are established and an ideal patient population is chosen, some of these techniques may be ready for human experimentation in the near future, with likely clinical implementation within the next decade. (Fertil Steril Ò 2020;113:500-9. Ó2020 by American Society for Reproductive Medicine.

Approaches and Technologies in Male Fertility Preservation

“…The cryopreserved testicular cells or tissue could be used for prepubertal human male fertility preservation with different approaches that are already used in rodents [27][28][29][30]. The main limitation of using autologous testicular tissue or cells in human therapy from cancer patients is the possibility of the presence of residual cancer cells, which may restore and evoke the disease.…”

“…The main limitation of this technology in humans is the possible contamination of testicular cells with cancer cells that may reintroduce malignancy to the patient after recovery. Today, there is no accurate and safe method that isolates pure SSCs from the testis of patients [50,62,63], in addition to the very small amount of testicular biopsy that could be used, it also contains very small numbers of these cells [4,14,24,27,29,58,64,65].…”

“…This microenvironment that provides optimal cell-cell interactions and the spatial environment for complete spermatogenesis is produced by the seminiferous tubules and interstitial compartment. This technology was proven successful in both autografting/xenografting and in vitro as organ culture [27][28][29][30]. Testicular tissue xenograft was successfully performed in immunodeficient mice while using testicular tissue from different species, which was grafted under the skin, producing complete spermatogenesis.…”

“…Recently, autologous grafting of cryopreserved prepubertal rhesus testis under the back skin or scrotal skin of castrated pubertal rhesus macaques matured to produce functional sperm and offspring [25]. Unfortunately, experiments involving the xenografting of human prepubertal cryopreserved testicular tissue into immunodeficient mice has not yet demonstrated the development of spermatid differentiation [25,27,[69][70][71][72]. It was shown that successful spermatogenesis in testicular tissue xenografts are affected by development through spermatogenesis, in addition to the timing of development and efficiency [64].…”

“…As mentioned above, the main benefit of using testicular fragments to develop spermatogenesis in vitro is the presence of testicular somatic cells and the three-dimension (3D) microenvironment that is suitable for the optimal development of SSCs to complete spermatogenesis [25][26][27][28][29]77]. Spermatogenesis development using organ culture to proceed to the meiotic stages was performed in the past without success [77][78][79][80].…”