Autologous Ectopic Grafting of Cryopreserved Testicular Tissue Preserves the Fertility of Prepubescent Monkeys That Receive Sterilizing Cytotoxic Therapy

Abstract

Boys faced with future sterility as a result of the need of a sterilizing cancer therapy might avoid this fate by engraftment of cryopreserved immature testicular tissue after therapy is completed. Efforts to address this important survivorship issue have been encouraged by reports of the long-term survival and proliferation of human spermatogonia after xenotransplant of cryopreserved immature testicular tissue into immunocompromised murine hosts. However, spermatogenic arrest at the pachytene spermatocyte stage that occurs in this situation has been associated with a failure in sperm production. In this study, we employed a prepubescent simian model to address the possibility that testicular tissue engraftment is insufficiently supported in the model to allow suitable maturation of germ cells. Briefly, we performed autologous orthotopic grafting of cryopreserved testicular tissue from four prepubescent and one pubescent rhesus monkeys after testicular irradiation and castration of the host animal. Five months after implantation of scrotal grafts, we determined that 3-7% of the autografts could be recovered with spermatogenesis proceeding through spermatozoa formation in 13-17% of the seminiferous tubules formed in the grafts. In contrast, Sertoli cell-only tubules were detected in parallel xenografts transplanted into immunocompromised mice. Our results demonstrate that cryopreservation of testicular tissue from prepubescent primates can maintain the fully functional capacity of spermatogonia to produce sperm, but that host conditions are critical for spermatogenic maturation. Further, our results establish an initial perspective on the quantity of cryopreserved material needed to ensure success in preserving fertility through testicular tissue grafts.

Regeneration of Leydig cells in ectopically autografted adult mouse testes

“…Testis autografting has been shown to be a feasible option for production of sperm in monkeys (Jahnukainen et al 2012). However, autologous immature testis grafts in the marmoset matured to meiosis, but normal serum testosterone level was not restored (Wistuba et al 2006).…”

Germ cell differentiation in cryopreserved, immature, Indian spotted mouse deer (Moschiola indica) testes xenografted onto mice

“…Since earlier studies have shown no difference in survival and development of xenografts in both castrated and intact (noncastrated) mouse recipients [25,26], cryopreserved testicular tissues were xenografted onto intact nude mice. Cryopreserved rhesus monkey testes could establish spermatogenesis in intact mice [27] but not in castrated mice [28], indicating that intact mice support spermatogenesis in cryopreserved testes. Seminal vesicle weight of recipients that were grafted with testis tissues that had been cryopreserved in either cryomedia was not different from the age-matched control, indicating normal serum testosterone levels.…”

Where are Oncofertility and Fertility Preservation Treatments Heading in 2016?

“…Presently, there are no reported human live births originating from sperm obtained from cryopreserved testes [33]. Although sperm can be obtained by grafting thawed testes [34] or transplanting spermatogonial stem cells into testes [35,36] in nonhuman primates, there is a risk of reintroducing malignant cells. These procedures are also quite invasive to patients.…”