Germ Cell Transplantation and Neospermatogenesis

Abstract

Spermatogonial stem cells (SSCs) are testis-specific stem cells, which are the foundation of spermatogenesis and male fertility. Transplanting germ cells including SSCs into the testis of an infertile recipient results in donor-derived spermatogenesis. Germ cell transplantation (GCT) is used to assay SSC activity and to quantify the SSC population. GCT also has the potential to treat infertility caused by cytotoxic treatment of juvenile patients for cancer or other cases of azoospermia. Transplanted SSCs move towards the basal compartment of the seminiferous tubule to colonize, and subsequently undergo mitosis and meiosis to generate sperm. The culture system for germ-line stem (GS) cells is well established for mice and rats, but it still remains challenging to produce complete spermatogenesis from GS cells in vitro. Testicular organ culture systems and emerging pluripotent stem cell technology are expected to provide in vitro spermatogenesis in the future. Successful GCT has been reported in many animal species and autologously in humans, though most xenogenic GCT led to incomplete spermatogenesis. Testicular tissue xenografting provides an alternative to GCT, in which grafted testicular tissue grows and produces xenogenic sperm in a mouse host. Testicular tissue xenografting is not only valuable for fertility preservation but also useful to investigate testicular growth and the regulatory system of spermatogenesis and to evaluate the toxicity of chemical substances and drugs on spermatogenesis. Genetic manipulation of germ cells followed by subsequent transplantation can be applied to basic biological study, animal transgenesis, and potentially gene modification therapy though this still remains controversial. Overall, GCT and testis tissue xenografting, in combination with testicular tissue banking, are expected to provide valuable options for fertility preservation.