DESCRIPTION (provided by applicant): Spermatogonial stem cells (SSCs) are adult stem cells in mammalian testes that maintain spermatogenesis and are essential for male fertility. Male infertility resulting from SSC loss after cancer treatments (e.g., chemotherapy and radiation) is a quality-of-life issue for many cancer survivors. In this proposal, we will test a nvel approach to preserving male fertility after cancer treatment that employs injections of the cytokine granulocyte colony-stimulating factor (G-CSF). In Aim 1, we will confirm that G-CSF administration prevents loss of spermatogenesis and fertility after chemotherapy and determine the optimal treatment regimen to maximize these beneficial effects. In Aim 2, we will determine whether G-CSF treatments act at the level of SSCs and will begin to address its protective mechanism of action. If found to be effective, G-CSF treatment would completely obviate the need for risky invasive interventions, and thus, has the potential to significantly improve the clinical paradigm for preserving male fertility after cancer treatment.

PUBLIC HEALTH RELEVANCE: Male infertility is a long-term side effect of childhood cancer treatments and preserving or restoring fertility in these patients is currently a major research focus. Promising experimental strategies addressing this unmet research need rely on surgically-based approaches that are expensive, complicated, and risky to the patient. In this proposal, we will test an exciting alternative strategy to preserve male fertility in cancer patiens that involves simple injections of G-CSF, an FDA-approved drug, and which has the potential to significantly improve the options available to doctors for managing/preventing male infertility after cancer treatment.