Genetic and Epigenetic Changes After Spermatogonial Stem Cell Culture and Transplantation

Men with testicular failure, either primary or secondary, have been shown to be interested in fertility preservation. Spermatogonial stem cell (SSC) transplantation is currently being investigated as a treatment for this. Currently this experimental technique consists of cryopreservation of a testicular biopsy prior to cancer treatment, followed by optional in vitro expansion of SSCs and auto transplantation after cancer treatment. This technique may restore the pool of SSCs resulting in restoration of spermatogenesis. While this technique has not been applied to humans due to its highly experimental nature and concerns of malignant contamination, animal studies have been successful. While the offspring obtained from SSCs appear to be healthy in rodent models, there is relatively little data on any genetic and epigenetic changes that occur in either the transplanted SSCs or offspring. In humans, male germ cells undergo unique and extensive chromatin and epigenetic remodeling soon after their destiny as a spermatocyte has been secured. Errors in this remodeling may cause altered genetic information to be transmitted to offspring, resulting in abnormalities. This is particularly pertinent for cancer patients as SSCs obtained from these men may have a predisposition for genetic instability even prior to starting gonadotoxic therapies. In this article, landmarks in the evolution of SSC transplantation are reviewed, along with presently known genetic, epigenetic, and imprinting abnormalities that may occur after in vitro propagation and transplantation.