Melatonin promotes goat spermatogonia stem cells (SSCs) proliferation by stimulating glial cell line-derived neurotrophic factor (GDNF) production in Sertoli cells

Oncotarget. 2016 Nov 22;7(47):77532-77542. doi: 10.18632/oncotarget.12720.

Abstract

Melatonin has been reported to be an important endogenous hormone for regulating neurogenesis, immunityand the biological clock. Recently, the effects of melatonin on neural stem cells (NSCs), mesenchymal stem cells(MSCs), and induced pluripotent stem cells(iPSCs) have been reported; however, the effects of melatonin on spermatogonia stem cells (SSCs) are not clear. Here, 1μM and 1nM melatonin was added to medium when goat SSCs were cultured in vitro, the results showed that melatonin could increase the formation and size of SSC colonies. Real-time quantitative PCR (QRT-PCR) and western blot analysis showed that the expression levels of SSC proliferation and self-renewal markers were up-regulated. Meanwhile, QRT-PCR results showed that melatonin inhibit the mRNA expression level of SSC differentiation markers. ELISA analysis showed an obvious increase in the concentration of GDNF (a niche factor secreted by Sertoli cells) in the medium when treated with melatonin. Meanwhile, the phosphorylation level of AKT, a downstream of GDNF-GFRa1-RET pathway was activated. In conclusion, melatonin promotes goat SSC proliferation by stimulating GDNF production in Sertoli cells.

Keywords: GDNF; Sertoli cells; melatonin; proliferation; spermatogonia stem cells (SSCs).

MeSH terms

  • Animals
  • Biomarkers
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Glial Cell Line-Derived Neurotrophic Factor / biosynthesis*
  • Goats
  • Humans
  • Male
  • Melatonin / pharmacology*
  • Sertoli Cells / drug effects*
  • Sertoli Cells / metabolism*
  • Signal Transduction / drug effects
  • Spermatogonia / cytology
  • Spermatogonia / drug effects*
  • Spermatogonia / metabolism*
  • Testis / cytology

Substances

  • Biomarkers
  • Glial Cell Line-Derived Neurotrophic Factor
  • Melatonin