Department of Dairy and Animal Science, The Pennsylvania State University, University Park, PA, USA.
Biol Reprod. 2011 Apr;84(4):639-45. doi: 10.1095/biolreprod.110.087320. Epub 2010 Nov 17.
Sustained spermatogenesis in adult males relies on the activity of spermatogonial stem cells (SSCs). In general, tissue-specific stem cell populations such as SSCs are influenced by contributions of support cells that form niche microenvironments. Previous studies have provided indirect evidence that several somatic cell populations and the interstitial vasculature influence SSC functions, but an individual orchestrator of niches has not been described. In this study, functional transplantation of SSCs, in combination with experimental alteration of Sertoli cell content by polythiouracil (PTU)-induced transient hypothyroidism, was used to explore the relationship of Sertoli cells with SSCs in testes of adult mice. Transplantation of SSCs from PTU-treated donor mice into seminiferous tubules of normal recipient mice revealed a greater than 3-fold increase in SSCs compared to those from testes of non-PTU-treated donors. In addition, use of PTU-treated mice as recipients for transplantation of SSCs from normal donors revealed a greater than 3-fold increase of accessible niches compared to those of testes of non-PTU treated recipient mice with normal numbers of Sertoli cells. Importantly, the area of seminiferous tubules bordered by interstitial tissue and percentage of seminiferous tubules associated with blood vessels was found to be no different in testes of PTU-treated mice compared to controls, indicating that neither the vasculature nor interstitial support cell populations influenced the alteration of niche number. Collectively, these results provide direct evidence that Sertoli cells are the key somatic cell population dictating the number of SSCs and niches in mammalian testes.
成年雄性的精子发生依赖于精原干细胞 (SSC) 的活性。一般来说,组织特异性干细胞群体,如 SSC,受到形成小生境微环境的支持细胞的贡献的影响。先前的研究提供了间接证据,表明几个体细胞群体和间质脉管系统影响 SSC 的功能,但尚未描述小生境的单个协调器。在这项研究中,通过聚硫代尿嘧啶 (PTU) 诱导的短暂甲状腺功能减退症对支持细胞含量进行实验性改变,结合 SSC 的功能移植,用于探索成年小鼠睾丸中 Sertoli 细胞与 SSC 之间的关系。将来自接受 PTU 处理的供体小鼠的 SSC 移植到正常受体小鼠的生精小管中,与来自未接受 PTU 处理的供体的 SSC 相比,SSC 的数量增加了 3 倍以上。此外,使用接受 PTU 处理的小鼠作为正常供体 SSC 移植的受体,与具有正常数量的 Sertoli 细胞的未接受 PTU 处理的受体小鼠的生精小管中的可及小生境相比,可及小生境的数量增加了 3 倍以上。重要的是,与接受 PTU 处理的小鼠相比,接受 PTU 处理的小鼠的生精小管的间质组织边界的生精小管面积和与血管相关的生精小管的百分比没有差异,表明血管或间质支持细胞群体均未影响小生境数量的改变。总之,这些结果提供了直接证据,表明 Sertoli 细胞是决定哺乳动物睾丸中 SSC 和小生境数量的关键体细胞群体。