ABSTRACT
It is well documented that γ-aminobutyric acid (GABA) system existed in reproductive organs. Recent researches showed that GABAA and GABAB receptors were present in testis and sperm, and might mediate the acrosome reaction induced by GABA and progesterone. GABA transporter I (GAT1) also existed in testis and sperm, but its physiological function was unknown. In the present study, we used GAT1 overexpressing mice to explore GAT1 function in male reproductive system. We found that the expression level of GAT1 continuously increased in wild-type mouse testis from 1 month to 2 months after birth. GAT1 overexpression in mouse affected testis development, which embodied reduced testis mass and slowed spermatogenesis in transgenic mice. Moreover, transgenic mice showed increase of the percentage of broken sperm. The further study revealed that the reproductive capacity was impaired in GAT1 overexpressing mice. In addition, testosterone level was significantly low in transgenic mice compared with that in wild-type mice. Our findings provided the first evidence that abnormal expression of GAT1 could result in dysgenesis, and indicated that GAT1 might be therapeutically targeted for contraception or dysgenesis treatment.
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Acknowledgements
We gratefully acknowledge Mrs. Xi Xia Zhou and Mrs. Hua Duo Zhang for help on maintaining mice; Professor Da Wang for his invaluable assistance with the histological techniques; Mr. Mao Hu Zhang for help on laboratory affairs. This project was supported by foundations from Chinese Academy of Sciences and Special Funds for Major State Basic Research Development program of China (G19990539).
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HU, J., ZHANG, J., MA, Y. et al. Impaired reproduction in transgenic mice overexpressing γ-aminobutyric acid transporter I (GAT1). Cell Res 14, 54–59 (2004). https://doi.org/10.1038/sj.cr.7290202
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DOI: https://doi.org/10.1038/sj.cr.7290202
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