Department of Cell Biology, Duke University Medical Center, Durham, NC, 27710, USA.
Department of Urology, Yokohama City University, Yokohama, Japan.
Nat Commun. 2020 Jan 2;11(1):40. doi: 10.1038/s41467-019-13879-8.
Spermatogonia, which produce sperm throughout the male lifetime, are regulated inside a niche composed of Sertoli cells, and other testis cell types. Defects in Sertoli cells often lead to infertility, but replacement of defective cells has been limited by the inability to deplete the existing population. Here, we use an FDA-approved non-toxic drug, benzalkonium chloride (BC), to deplete testis cell types in vivo. Four days after BC administration, Sertoli cells are preferentially depleted, and can be replaced to promote spermatogenesis from surviving (host) spermatogonia. Seven days after BC treatment, multiple cell types can be engrafted from fresh or cryopreserved testicular cells, leading to complete spermatogenesis from donor cells. These methods will be valuable for investigation of niche-supporting cell interactions, have the potential to lead to a therapy for idiopathic male infertility in the clinic, and could open the door to production of sperm from other species in the mouse.
精原细胞在男性的整个生命周期中产生精子，它们受到由支持细胞和其他睾丸细胞类型组成的小生境的调控。支持细胞的缺陷常常导致不育，但由于无法耗尽现有细胞群体，因此对缺陷细胞的替代受到限制。在这里，我们使用一种 FDA 批准的无毒药物苯扎氯铵（BC）在体内耗尽睾丸细胞类型。BC 给药后 4 天，支持细胞优先耗尽，并且可以被替换以促进来自存活（宿主）精原细胞的精子发生。BC 处理后 7 天，可以从新鲜或冷冻保存的睾丸细胞中移植多种细胞类型，从而导致来自供体细胞的完全精子发生。这些方法对于研究小生境支持细胞相互作用将非常有价值，有可能在临床上为特发性男性不育症提供治疗方法，并为在小鼠中从其他物种产生精子开辟道路。
