Double sex and mab-3 related transcription factor 1 regulates differentiation and proliferation in dairy goat male germline stem cells

J Cell Physiol. 2018 Mar;233(3):2537-2548. doi: 10.1002/jcp.26129. Epub 2017 Sep 13.

Abstract

The protein encoded by double sex and mab-3 related transcription factor 1 (Dmrt1) gene contains a double sex/mab-3 domain, which was considered as one of the most conservative structures in sex determination. However, its effect on spermatogenesis of dairy goat spermatogonial stem cells (SSCs) remains to be clarified. For the first time, the roles of Dmrt1 in spermatogenesis of livestock are highlighted. Here, we investigated the expression pattern of Dmrt1 in the testes of dairy goats. Dmrt1 primarily located in undifferentiated SSCs. Moreover, Dmrt1 enhanced differentiation and proliferation of mGSCs. On the contrary, the level of meiosis was down-regulated, as Dmrt1 determines whether SSCs undergo mitosis and spermatogonial differentiation or meiosis. In the busulfan-treated mice testes, Dmrt1 repair germ cell damage was emphasized as well. Our results exposed that Dmrt1 maintenance mGSCs in two ways: facilitating proliferation and self-renewal of SSCs; and reducing the inflammatory response caused by reproductive injury. These findings identify a central role for Dmrt1 in controlling population stability and injury restoring of SSCs.

Keywords: Dmrt1; goat; male germline stem cells (mGSCs); proliferation; self-renewal.

MeSH terms

  • Adult Germline Stem Cells / drug effects
  • Adult Germline Stem Cells / metabolism*
  • Adult Germline Stem Cells / pathology
  • Animals
  • Busulfan / toxicity
  • Cell Differentiation* / drug effects
  • Cell Proliferation* / drug effects
  • Cell Self Renewal* / drug effects
  • Cells, Cultured
  • Dairying*
  • Gene Expression Regulation, Developmental
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Goats / genetics
  • Goats / metabolism*
  • Macrophage Colony-Stimulating Factor / metabolism
  • Male
  • Meiosis
  • Mitosis
  • Promyelocytic Leukemia Zinc Finger Protein / metabolism
  • Signal Transduction
  • Spermatogenesis* / drug effects
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection
  • Tretinoin / pharmacology

Substances

  • DMRT1 protein
  • Glial Cell Line-Derived Neurotrophic Factor
  • Promyelocytic Leukemia Zinc Finger Protein
  • Transcription Factors
  • Tretinoin
  • Macrophage Colony-Stimulating Factor
  • Busulfan