Center for Reproductive Biology, School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
Center for Reproductive Biology, School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
Curr Top Dev Biol. 2014;107:235-67. doi: 10.1016/B978-0-12-416022-4.00009-3.
Sperm have a vital role in the continuity of a species by contributing genetic information to the next generation. Production of these specialized gametes in numbers sufficient to confer normal fertility occurs via cycling of the spermatogenic lineage, a process referred to as spermatogenesis. Continuity relies on the activities of a self-renewing reservoir of spermatogonial stem cells (SSCs) from which progenitors will arise that transiently amplify in number before committing to a pathway of terminal differentiation. A primary population of SSCs is established during neonatal development from a pool of quiescent gonocyte precursors that forms in embryogenesis. Disruption of this process has dire consequences on maintenance of a cycling spermatogenic lineage in adulthood. At present, the molecular mechanisms underlying initial formation of the SSC pool are largely undefined. However, several transcription factors and posttranscriptional regulators have been identified as important regulators of SSC self-renewal from studies with mutant mouse models and experimental manipulation within primary cultures of mouse SSCs. Importantly, loss of function of these self-renewal factors may be underlying causes of infertility. Furthermore, disruption in the establishment of the SSC state within gonocytes or misregulation of self-renewal may manifest as testicular germ cell tumors in postnatal life.
精子在物种的连续性中起着至关重要的作用，通过将遗传信息贡献给下一代。这些专门的配子的数量足以产生正常的生育能力，这是通过精原细胞系的循环发生的，这个过程被称为精子发生。连续性依赖于自我更新的精原干细胞（SSC）库的活动，这些干细胞库中的祖细胞在进行终末分化之前会短暂扩增。一个主要的 SSC 群体是在新生儿发育过程中从胚胎发生中形成的静止性精原细胞前体细胞池中建立起来的。如果这个过程受到干扰，成年后循环精原细胞系的维持就会受到严重影响。目前，SSC 库最初形成的分子机制在很大程度上还不清楚。然而，已经有几个转录因子和转录后调节因子被确定为 SSC 自我更新的重要调节因子，这是通过对突变小鼠模型的研究和对小鼠 SSC 原代培养的实验操作得出的。重要的是，这些自我更新因子的功能丧失可能是不育的根本原因。此外，在精原细胞中 SSC 状态的建立受到干扰或自我更新的失调，可能会在出生后表现为睾丸生殖细胞肿瘤。
