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GABA exists as a negative regulator of cell proliferation in spermaogonial stem cells

An Erratum to the article to this article was published on 29 December 2013

Abstract

γ-amino butyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian central nervous system. GABA is also found in many peripheral tissues, where it has important functions during development. Here, we identified the existence of the GABA system in spermatogonial stem cells (SSCs) and found that GABA negatively regulates SSC proliferation. First, we demonstrated that GABA and its synthesizing enzymes were abundant in the testes 6 days postpartum (dpp), suggesting that GABA signaling regulates SSCs function in vivo. In order to directly examine the effect of GABA on SSC proliferation, we then established an in vitro culture system for long-term expansion of SSCs. We showed that GABAA receptor subunits, including α1, α5, β1, β2, β3 and γ3, the synthesizing enzyme GAD67, and the transporter GAT-1, are expressed in SSCs. Using phosphorylated histone H3 (pH3) staining, we demonstrated that GABA or the GABAAR-specific agonist muscimol reduced the proliferation of SSCs. This GABA regulation of SSC proliferation was shown to be independent of apoptosis using the TUNEL assay. These results suggest that GABA acts as a negative regulator of SSC proliferation to maintain the homeostasis of spermatogenesis in the testes.

Abbreviations

bFGF:

basic fibroblast growth factor

CSF-1:

colony-stimulating factor 1

dpp:

days postpartum

GABA:

γ-amino butyric acid

GDNF:

lial cell line-derived neurotrophic factor

MEF:

mouse embryonic fibroblasts

pH3:

phosphorylated histone H3

SSCs:

spermatogonial stem cells

TUNEL:

terminal deoxynucleotidyl transferase dUTP nick end labeling These authors contributed equally to this paper

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Correspondence to Yiping Li.

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Du, Y., Du, Z., Zheng, H. et al. GABA exists as a negative regulator of cell proliferation in spermaogonial stem cells. Cell Mol Biol Lett 18, 149–162 (2013). https://doi.org/10.2478/s11658-013-0081-4

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Keywords

  • Seminiferous Tubule
  • Muscimol
  • Molecular Biology Letter
  • Spermatogonial Stem Cell
  • Gaba System