title: GABA exists as a negative regulator of cell proliferation in spermatogonial stem cells. [corrected].
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.
authors: State Key Laboratory of Cell Biology, Shanghai Key Laboratory for Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Yong
authors: Y
authors: Du
authors: Zhao
authors: Z
authors: Du
authors: Hongping
authors: H
authors: Zheng
authors: Dan
authors: D
authors: Wang
authors: Shifeng
authors: S
authors: Li
authors: Yuanchang
authors: Y
authors: Yan
authors: Yiping
authors: Y
authors: Li
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D015398:Signal Transduction; D013093:Spermatogonia / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D013737:Testis / Q000166:cytology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2