Dmrt1 regulates the immune response by repressing the TLR4 signaling pathway in goat male germline stem cells
Yudong Wei, 西北农林科技大学动物医学院，陕西干细胞工程技术研究中心，陕西 杨凌712100，中国, Xiaomin Du, Donghui Yang, Fanglin Ma, Xiuwei Yu, Meng-Fei Zhang, Na Li, Sha Peng, Mingzhi Liao, Guangpeng Li, Chunling Bai, Weishuai Liu, Jinlian Hua, 西北农林科技大学生命科学学院，陕西 杨凌712100，中国, 内蒙古大学生命科学学院，草原家畜生殖调控与繁育国家重点实验室，内蒙古 呼和浩特010021，中国, 杨凌示范区医院病理科，陕西 杨凌712100，中国
Abstract
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.