Spermatogonial stem cell biomarkers: improved outcomes of spermatogonial transplantation in male fertility restoration?

Human male infertility has become a major health and social concern worldwide, and this is being increasingly realized as cancer survival rates improve. It is estimated that the prevalence of cancer survivors among young adults will be one in 250 persons by 2010 [1]. With improving cancer survival rates, male infertility is expected to escalate because anticancer treatments greatly affect spermatogenesis [2]. Indeed, an estimated 50% of leukemia survivors become infertile following treatment [3]. As a result, restoration of fertility is, and will increasingly become, an important quality-oflife issue for cancer survivors. Currently, semen cyropreservation is the only option to preserve male fertility through assisted reproductive technologies; however, the success rate of this approach is as low as 25% [4]. Importantly, this strategy is not applicable to prepubertal patients who at the time of anticancer treatments do not produce mature sperm. Therefore, new technologies need to be developed. Self-renewing systems, such as the epidermis, hematopoiesis and spermatogenesis, undergo continuous cell turnover every day and, as such, are supported by respective adult stem cells. Spermatogonial stem cells (SSCs) are the supporting stem cells of spermatogenesis and, similar to other adult stem cells, are functionally defined by their ability to produce differentiated cells, as well as self-renew to maintain the stem cell pool, thereby regenerating and maintaining their respective adult tissue [5]. However, unlike other adult stem cells, SSCs are unique in that they transmit genetic information to future progeny and are, thus, critical to sustain the health of our society over generations. Owing to their functional def inition, stem cells are directly identified through transplantation, which assesses their regenerative ability. In this manner, SSCs are assayed through spermatogonial transplantation whereby testis cells are injected into the seminiferous tubules of an infertile recipient testis, resulting in spermatogenesis regeneration [6]. While this has primarily been used as an assay for rodent SSCs, the scheme of spermatogonial transplantation evidently suggests potential clinical approaches to regenerate spermatogenesis and restore male fertility, especially in sterile cancer survivors. Much like autologous hematopoietic stem-cell transplantations from umbilical cord, bone marrow or peripheral blood to regenerate a depleted hematopoietic system [7], SSCs isolated from a patient prior to potentially sterilizing anticancer treatments can be reintroduced back into the patient following treatment. This spermatogonial transplantation-based approach is conceptually straightforward and apparently requires only minimal knowledge of the molecular biology of human SSCs (e.g., biomarkers); one clinical trial of spermatogonial transplantation into human testis has already been conducted [8]. It is believed, however, that the identification of SSC biomarkers Jonathan R Yeh Department of Obstetrics and Gynecology and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada Tel. : +1 514 934 1934 ext. 35250 Fax: +1 514 843 1662 jonathan.yeh@ mail.mcgill. ca