Endocrine Abstracts (2006) 11 S45

Stem cell therapeutic approaches to male infertility

S Schlatt

University of Pittsburgh School of Medicine, Pittsburgh, United States.

The testis provides stem cell niches which are populated by spermatogonial stem cells. The seminiferous epithelium is the exclusive site where germline cells are proliferating and entering meiosis in the adult organism. The existence of stem cells offers clinically relevant options for preservation and restoration of male fertility. New approaches based on male germ cell transplantation and testicular tissue grafting can be applied to generate sperm. Germ cell transplantation relies on removal of the stem cell from the donor’s testicular niche. The stem cell can then be transferred back into the donor’s testis or into different testes which provide the suitable microenvironment to generate sperm from the transplanted stem cell. In contrast, grafting can be considered as a transplantation of the stem cell in conjunction with its niche. Germ cell transplantation of human spermatogonia into mouse testes revealed that the spermatogonial stem cells colonize the mouse testes but are not able to differentiate and complete spermatogenesis. This indicates that stem cell recognition and expansion are conserved throughout evolution but also reveals that the early steps in spermatogenesis differ between rodents and primates. This might be due to the fact that the primate testis contains stem cells and progenitors while a progenitor spermatogonium does not exist in rodents. Monkey experiments showed that germ cell transplantation as an autologous approach can be applied in primates. Ectopic xeno-grafting of testicular tissue was applied to generate fertile sperm from a variety of species. Newborn or juvenile testicular tissue from rodents, domestic animals and primates was grafted into the back skin of immunodeficient mice and developed up to qualitatively complete spermatogenesis. The sperm were successfully used to create progeny. We recently showed that autologous grafting can be applied to stimulate testicular development in marmosets. Xenografting of adult human testes, however, revealed only limited success to maintain testicular tissue. We conclude that the rapid progress in the development of novel experimental strategies to generate sperm from cryopreserved spermatogonial stem cells or testicular tissue will lead to many new options for fertility preservation.

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