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

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

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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(ChlP-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.

Dmrt1SpermatogenesisOrchitisSpry1NF-κB

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

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College of Veterinary Medicine,Shaanxi Centre of Stem Cells Engineering & Technology,Northwest A&F University,Yangling,Shaanxi 712100,China

Center of Reproductive Medicine,Amsterdam Research Institute Reproduction and Development,Academic Medical Center,University of Amsterdam 1105AZ,Amsterdam,Netherlands

Key Laboratory for Mammalian Reproductive Biology and Biotechnology,Ministry of Education,Inner Mongolia University,Hohhot,Inner Mongolia 010021,China

Key Laboratory of Livestock Biology,Northwest A&F University,Yangling,Shaanxi 712100,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Key Research and Development Program of ChinaProgram of Shaanxi Province Science and Technology Innovation TeamMajor Projects of Natural Science Foundation of Inner Mongolia Autonomous RegionKey Research and Development Program of Shaanxi ProvinceKey Technologies Demonstration of Animal Husbandry in Shaanxi Province

32072806315723992022YFD13022012019TD-0362020ZD102022NY-04420221086

2023

10.24272/j.issn.2095-8137.2022.440

动物学研究
中国科学院昆明动物研究所 中国动物学会

动物学研究

CSTPCDCSCD
影响因子：0.582
ISSN：0254-5853
年,卷(期)：2023.44(3)
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