Double sex and mab-3-related transcription factor 1 (Dmrt1), which is expressed in goat male germline stem cells (mGSCs) and Sertoli cells, is one of the most conserved transcription factors involved in sex determination. In this study, we highlighted the role of Dmrt1 in balancing the innate immune response in goat mGSCs. Dmrt1 recruited promyelocytic leukemia zinc finger (Plzf), also known as zinc finger and BTB domain-containing protein 16 (Zbtb16), to repress the Toll-like receptor 4 (TLR4)-dependent inflammatory signaling pathway and nuclear factor (NF)-κB. Knockdown of Dmrt1 in seminiferous tubules resulted in widespread degeneration of germ and somatic cells, while the expression of proinflammatory factors were significantly enhanced. We also demonstrated that Dmrt1 stimulated proliferation of mGSCs, but repressed apoptosis caused by the immune response. Thus, Dmrt1 is sufficient to reduce inflammation in the testes, thereby establishing the stability of spermatogenesis and the testicular microenvironment.
雄性生殖干细胞 (male Germ Stem Cell, mGSCs)，同样被称作精原干细胞 (Spermatogonial Stem Cells, SSCs)，是位于睾丸曲细精管基底膜上，既能通过自我更新维持自身群体数量的稳定，又能在体内定向分化并最终形成精子的一类成体干细胞。雄性生殖干细胞可以作为研究精子发生、减数分裂调控和细胞重编程的一个理想体外模型。Double sex and mab-3 related transcription factor 1 (DMRT1) 基因编码的蛋白质包含一个double sex/mab-3结构域，无论是在脊椎动物或者无脊椎动物中，这个最保守的结构域都会参与个体的性别决定过程。转录因子Dmrt1在奶山羊雄性生殖干细胞（mGSCs）和支持细胞（Sertoli cells）中都存在表达。在这项研究中，我们探究了Dmrt1在奶山羊mGSCs中免疫应答作用。Dmrt1通过募集转录因子Plzf（Promyelocytic Leukemia Zinc Finger，Plzf；又称为zinc finger and BTB domain-containing protein 16，Zbtb16）以抑制Toll样受体4（Toll-like receptor 4，TLR4）依赖性的炎症信号通路和核因子NF- κB的表达，从而降低雄性生殖干细胞中炎症反应的发生。我们在曲细精管中敲低Dmrt1导致了生殖细胞和体细胞的丢失，并发现促炎因子TNFα及IL-6的表达量上调。同时我们发现Dmrt1可以促进mGSCs的自我更新和增殖，并抑制由炎症反应引起的雄性生殖干细胞的凋亡。综合以上结果表明，DMRT1在促进雄性生殖干细胞自我更新及维持睾丸内环境稳态中的重要功能，提供了治疗睾丸生殖缺陷疾病的新思路。.
Keywords: Dmrt1; Goat; Male germline stem cells (mGSCs); Plzf, Immune response.