In testis, a rare undifferentiated germ cell population with the capacity to regenerate robustly and support spermatogenesis, is defined as spermatogonial progenitor cells (SPCs) population. As a widely used drug for tumor therapy or bone marrow transplantation, busulfan has a severe side effect on SPCs population and causes a consequent infertility. Recently, accumulating evidence revealed the protective role of autophagy in stem cell maintenance under exogenous stress. To better understand the role of autophagy in SPCs fates, we investigated the potential function of autophagy in SPCs under busulfan stress, and found that treatment of busulfan induced the formation of autophagic vesicles and autophagosomes in mouse SPCs. Subsequently, a connection of autophagy and SPCs maintenance and survival was demonstrated in a dose-dependent manner. Moreover, mTOR was identified as an essential factor for autophagy in SPCs with a complicated mechanism: (1) mTOR is phosphorylated by AKT to activate its target genes, p70s6 kinase, resulting in the inhibition of autophagy during short-term busulfan treatment. (2) mTOR mediates autophagy with p53 together, to regulate the fate of SPCs. Collectively, observations from this study indicate that moderate autophagy effectively protects SPCs from the stress of chemotherapy, which may provide an important hint for fertility protection in clinic.

在睾丸中，一种罕见的未分化生殖细胞群具有强大的再生能力和支持精子发生的能力，被定义为精原祖细胞 (SPC) 群。作为一种广泛用于肿瘤治疗或骨髓移植的药物，白消安对 SPCs 群体具有严重的副作用，并导致随之而来的不孕症。最近，越来越多的证据揭示了自噬在外源性压力下干细胞维持中的保护作用。为了更好地了解自噬在 SPC 命运中的作用，我们研究了白消安应激下 SPC 中自噬的潜在功能，发现白消安的处理诱导了小鼠 SPC 中自噬囊泡和自噬体的形成。随后，以剂量依赖性方式证明了自噬与 SPC 维持和存活之间的联系。此外，mTOR 被确定为 SPC 中自噬的重要因素，其机制复杂：（1）mTOR 被 AKT 磷酸化以激活其靶基因 p70s6 激酶，导致短期白消安治疗期间自噬受到抑制。(2) mTOR与p53共同介导自噬，调节SPC的命运。总的来说，这项研究的观察表明，适度的自噬可以有效地保护 SPCs 免受化疗的压力，这可能为临床上的生育保护提供重要提示。来调节 SPC 的命运。总的来说，这项研究的观察表明，适度的自噬可以有效地保护 SPCs 免受化疗的压力，这可能为临床上的生育保护提供重要提示。来调节 SPC 的命运。总的来说，这项研究的观察表明，适度的自噬可以有效地保护 SPCs 免受化疗的压力，这可能为临床上的生育保护提供重要提示。