Xenografting of adult mammalian testis tissue

Abstract

Xenografting of testis tissue from immature males from several mammalian species to immunodeficient mouse hosts results in production of fertilization-competent sperm. However, the efficiency of testis tissue xenografting from adult donors has not been critically evaluated. Testis tissue xenografting from sexually mature animals could provide an option to preserve the genetic material from valuable males when semen for cryopreservation cannot be collected. To assess the potential use of this technique for adult individuals, testes from adult animals of six species (pig, goat, cattle, donkey, horse and rhesus monkey) were ectopically grafted to host mice. Grafts were recovered and analyzed at three time points: less than 12 weeks, between 12 and 24 weeks and more than 24 weeks after grafting. Histological analysis of the grafts revealed effects of species and donor tissue maturity: all grafts from species with greater daily sperm production (pig and goat) were found to have degenerated tubules or grafts were completely degenerated. None of the xenografts from mature adult bull and monkeys contained differentiated spermatogenic cells when examined more than 12 weeks post-grafting but tubules with Sertoli cells only remained. In grafts from a young adult bull, Sertoli cells persisted much longer than with the mature adult grafts. In grafts from a young adult horse, spermatogenesis proceeded to meiosis. In grafts from a young adult donkey and monkey, however, complete spermatogenesis was found in the grafts. These results show that testis tissue grafts from mature adult donors did not support germ cell differentiation but seminiferous tubules with Sertoli cells only survived in some species. The timing and progression of tubular degeneration after grafting of adult testis tissue appear to be related to the intensity of spermatogenesis at the time of grafting. Testis tissue from sub-adult donors survives better as xenograft than tissue from mature adult donors, and complete spermatogenesis can occur albeit with species-specific differences.

Regeneration of Leydig cells in ectopically autografted adult mouse testes

“…Degeneration of graft testicular tissue could have possibly occurred because of the absence of the natural scrotal environment and exposure to hyperthermic conditions at the ectopic site of grafting. The adult testes of species with high daily sperm production such as pig and goat after xenografting to mice recipients showed a complete degeneration of tubules and grafts (Arregui et al 2008). However in species such as bull and monkeys where daily sperm production is low, xenografted adult testes had either degenerated tubules or …”

“…Survival of only seminiferous tubules with Sertoli cells was seen in mature bull and monkey donor grafts; however, complete spermatogenesis was observed when the donor graft tissue was not completely mature (Arregui et al 2008). No germ cell differentiation was observed in adult human testes xenografted onto mouse hosts (Geens et al 2006.…”

“…Successful generation of sperm from xenografts of immature testes from mice, hamsters, monkeys , bulls (Oatley et al 2005), pigs, goats (Honaramooz et al 2002), cats (Snedaker et al 2004), buffaloes (Reddy et al 2012) and mouse hosts has already been reported. Previous studies have shown that xenografted testis tissue from sexually mature donors is less successful than that from sexually immature donors (Arregui et al 2008). Moreover, complete spermatogenesis has been reported to be absent in the xenografts that contained post-meiotic germ cells at the time of grafting in all species analyzed to date, and most of the mature donor grafts regressed or were found to contain degenerated tubules , Geens et al 2006, Arregui et al 2008, Abrishami et al 2010.…”

“…Previous studies have shown that xenografted testis tissue from sexually mature donors is less successful than that from sexually immature donors (Arregui et al 2008). Moreover, complete spermatogenesis has been reported to be absent in the xenografts that contained post-meiotic germ cells at the time of grafting in all species analyzed to date, and most of the mature donor grafts regressed or were found to contain degenerated tubules , Geens et al 2006, Arregui et al 2008, Abrishami et al 2010. Spermatogenesis was arrested at meiosis in grafts from mature horse (Rathi et al 2006), dog (Abrishami et al 2010) and photoregressed hamster testes .…”

Can we grow sperm? A translational perspective on the current animal and human spermatogenesis models

“…36 For still unknown reasons, mature testis tissue grafts do not support germ cell differentiation as well as immature testis tissue grafts in xenograft models. 38 To further demonstrate this finding, Yu and colleagues 39 transplanted fetal (20-26 weeks) human testicular tissue subcutaneously onto an immunodeficient nude mouse and demonstrated that the xenograft could survive for more than 135 days. These fetal grafts did extremely well; with increased graft weight, Sertoli cell differentiation and germ cell migration were demonstrated over time.…”