Transcription factor Dmrt1 triggers the SPRY1-NF-κB pathway to maintain testicular immune homeostasis and male fertility  

作　　者：Meng-Fei Zhang Shi-Cheng Wan Wen-Bo Chen Dong-Hui Yang Wen-Qing Liu Ba-Lun Li Aili Aierken Xiao-Min Du Yun-Xiang Li Wen-Ping Wu Xin-Chun Yang Yu-Dong Wei Na Li Sha Peng Xue-Ling Li Guang-Peng Li Jin-Lian Hua 

机构地区：[1]College of Veterinary Medicine,Shaanxi Centre of Stem Cells Engineering&Technology,Northwest A&F University,Yangling,Shaanxi 712100,China [2]Center of Reproductive Medicine,Amsterdam Research Institute Reproduction and Development,Academic Medical Center,University of Amsterdam 1105AZ,Amsterdam,Netherlands [3]Key Laboratory for Mammalian Reproductive Biology and Biotechnology,Ministry of Education,Inner Mongolia University,Hohhot,Inner Mongolia 010021,China [4]Key Laboratory of Livestock Biology,Northwest A&F University,Yangling,Shaanxi 712100,China

出　　处：《Zoological Research》2023年第3期505-521,共17页动物学研究（英文）

基　　金：supported by the National Natural Science Foundation of China(32072806,31572399);National Key Research and Development Program of China(2022YFD1302201);Program of Shaanxi Province Science and Technology Innovation Team(2019TD-036);Major Projects of Natural Science Foundation of Inner Mongolia Autonomous Region(2020ZD10);Key Research and Development Program of Shaanxi Province(2022NY-044);Key Technologies Demonstration of Animal Husbandry in Shaanxi Province(20221086)。

摘　　要：Bacterial or viral infections,such as Brucella,mumps virus,herpes simplex virus,and Zika virus,destroy immune homeostasis of the testes,leading to spermatogenesis disorder and infertility.Of note,recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells,leading to male reproductive dysfunction.Due to the many side effects associated with antibiotic therapy,finding alternative treatments for inflammatory injury remains critical.Here,we found that Dmrt1 plays an important role in regulating testicular immune homeostasis.Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells.Chromatin immunoprecipitation sequencing(ChIP-seq)and RNA sequencing(RNA-seq)revealed that Dmrt1 positively regulated the expression of Spry1,an inhibitory protein of the receptor tyrosine kinase(RTK)signaling pathway.Furthermore,immunoprecipitation-mass spectrometry(IP-MS)and co-immunoprecipitation(Co-IP)analysis indicated that SPRY1 binds to nuclear factor kappa B1(NF-κB1)to prevent nuclear translocation of p65,inhibit activation of NF-κB signaling,prevent excessive inflammatory reaction in the testis,and protect the integrity of the blood-testis barrier.In view of this newly identified Dmrt1-Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis,our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.

关 键 词：DMRT1 SPERMATOGENESIS ORCHITIS Spry1 NF-κB 

分 类 号：S852.4[农业科学—基础兽医学]