G-CSF prevents male infertility after chemotherapy.

描述(申请人提供)：精原干细胞(SSCs)是哺乳动物睾丸中的成体干细胞，维持精子发生，对男性生育能力至关重要。癌症治疗(如化疗和放射治疗)后SSC丢失导致的男性不育是许多癌症幸存者的生活质量问题。在这项提案中，我们将测试一种新的癌症治疗后保留男性生育能力的方法，即注射细胞因子粒细胞集落刺激因子(G-CSF)。在目标1中，我们将确认G-CSF的应用可以防止化疗后精子生成和生育能力的丧失，并确定最优的治疗方案以最大限度地发挥这些有益效果。在目标2中，我们将确定G-CSF治疗是否在SSCs水平起作用，并将开始解决其保护作用机制。如果证明有效，G-CSF治疗将完全消除危险的侵入性干预的需要，因此，有可能显著改善癌症治疗后保留男性生育能力的临床范例。

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.