4.6 Article

Dmrt1 regulates the immune response by repressing the TLR4 signaling pathway in goat male germline stem cells

Journal

ZOOLOGICAL RESEARCH
Volume 42, Issue 1, Pages 14-27

Publisher

SCIENCE PRESS
DOI: 10.24272/j.issn.2095-8137.2020.186

Keywords

Male germline stem cells (mGSCs); Goat; Dmrt1; Plzf; Immune response

Categories

Funding

  1. China National Basic Research Program [2016YFA0100203]
  2. National Natural Science Foundation of China [31572399, 32072806, 32072815, 32002246]
  3. State Key Lab of Reproductive Regulation & Breeding of Grassland Livestock [SKL-OT-201801]
  4. Science and Technology Major Project of Inner Mongolia Autonomous Region of China [ZDZX2018065]
  5. Shaanxi Province Science and Technology Innovation Team [2019TD-036]

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The study emphasized the role of Dmrt1 in balancing the innate immune response in goat mGSCs by repressing inflammatory signaling pathways, thus maintaining the stability of germline and somatic cells.
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)-kappa B. 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.

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