4.3 Article

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

Journal

ONCOTARGET
Volume 7, Issue 47, Pages 77532-77542

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.12720

Keywords

melatonin; spermatogonia stem cells (SSCs); GDNF; Sertoli cells; proliferation

Funding

  1. Program of National Natural Science Foundation of China [31272518, 31572399]
  2. China National Basic Research Program [2016YFA0100203]
  3. National Major Project for Production of Transgenic Breeding [2014ZX08007-002]
  4. National High Technology Research and Development Program of China [SS2014AA021605]
  5. Key Project of the Chinese Ministry of Science and Technology [2013CB967401]
  6. Program of the Shaanxi Province [2015NY157]

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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, 1 mu M 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.

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