γ-Aminobutyric acid transporter (GAT1) overexpression in mouse affects the testicular morphology

Hua, Ying; Hu, Jia; Zhou, Xinyu; Mei, Zhanlong; Fei, Jian; Guo, Li

doi:10.1038/sj.cr.7290036

Cited by 28 publications

(27 citation statements)

References 6 publications

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“…GAD67 mRNA, but not GAD65, was expressed in SSCs. GAT-1, the only membrane GABA transporter found in the testes and sperm of rodents [12,25], was also detected in SSCs (Fig. 3A).…”

Section: Gaba Signaling Components Are Expressed In Mouse Sscsmentioning

confidence: 97%

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

Zheng

et al. 2013

Cellular and Molecular Biology Letters

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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 GABA A 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 GABA A R-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.

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“…GAD67 mRNA, but not GAD65, was expressed in SSCs. GAT-1, the only membrane GABA transporter found in the testes and sperm of rodents [12,25], was also detected in SSCs (Fig. 3A).…”

Section: Gaba Signaling Components Are Expressed In Mouse Sscsmentioning

confidence: 97%

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

Zheng

et al. 2013

Cellular and Molecular Biology Letters

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“…The height of the seminiferous epithelium was calculated by subtracting the lumen diameter from the tubule diameter. For each animal 150 tubules were analyzed [23,24].…”

Section: Morphometrymentioning

confidence: 99%

The effect of zinc oxide nanoparticles on mouse spermatogenesis

Talebi

Khorsandi

Moridian³

2013

J Assist Reprod Genet

123

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Objective To evaluate the effects of zinc oxide nanoparticles on mouse spermatogenesis. Methods Thirty two adult male NMRI mice were used. Experimental Groups (ZNP-1-ZNP-3) received one of the following treatments daily for 35 days: 5, 50 and 300 mg/kg zinc oxide nanoparticles respectively. Control group received only distilled water. Epididymal sperm parameters, testicular histopathology, morphometric analysis and spermatogenesis assessments were performed for evaluation of the zinc oxide nanoparticles effects on testis. Results Epididymal sperm parameters including sperm number, motility and percentage of abnormality were significantly changed in 50 and 300 mg/kg zinc oxide nanoparticles treated mice (p<0.01). Histopathological criteria such as epithelial vacuolization, sloughing of germ and detachment were significantly increased in 50 and 300 mg/kg zinc oxide nanoparticles treated mice (p<0.001). 300 mg/kg zinc oxide nanoparticles induced formation of multinucleated giant cells in the germinal epithelium. 50 and 300 mg/kg zinc oxide nanoparticles also caused a significant decrease in seminiferous tubule diameter, seminiferous epithelium height and maturation arrest (p<0.001). Conclusion Zinc oxide nanoparticles act as testicular toxicant and further studies are needed to establish its mechanism of action upon spermatogenesis.

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“…Recent findings demonstrated that GAT1 also expresses in rat testis, and is involved in the acrosome reaction, an essential fertilization event, and that overexpression of GAT1 in transgenic mice affects the testicular morphology [2], [3]. The same primers (P1 and P2) were used to identify GAT1 transcriptional starting site in adult rat testis.…”

Section: Gat1 Transcriptional Starting Site In Rat Testismentioning

confidence: 99%

“…Since GABA is the predominant inhibitory neurotransmitter in CNS, abnormality of GATs has a direct relationship with certain kinds of nervous disorders, such as epilepsy and cognitive deterioration. Recent studies indicated that GAT1 also expresses in rat testis and is involved in the acrosome reaction [2], [3]. GAT1 expresses widely in nervous system and non-nervous tissues, and takes part in different physiological processes.…”

Section: Introductionmentioning

confidence: 99%

GABA transporter 1 transcriptional starting site exhibiting tissue specific difference

et al. 2001

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GABA transporter 1(GAT1) takes important roles in multiple physiological processes through the uptake and release of GABA, but the regulation of GAT1 gene expression in different tissues is rarely known. To address the question, first, 5 Rapid amplification of cDNA end (RACE) was used to determine GAT1 transcriptional starting sites in neonatal mouse cerebral cortex and intestine, adult mouse brain and adult rat testis. The products of 5 RACE were confirmed by DNA sequencing. We found that the transcript of GAT1 in neonatal mouse cerebral cortex and adult mouse brain starts at the same site (inside of exon 1), while in mouse intestine, GAT1 starts transcription in intron 1, and in rat testis, the transcript of GAT1 has an additional untranslation exon to the 5 direction.

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γ-Aminobutyric acid transporter (GAT1) overexpression in mouse affects the testicular morphology

Cited by 28 publications

References 6 publications

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

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

The effect of zinc oxide nanoparticles on mouse spermatogenesis

GABA transporter 1 transcriptional starting site exhibiting tissue specific difference

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