Impaired reproduction in transgenic mice overexpressing γ-aminobutyric acid transporter I (GAT1)

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.

作 者： Jia Hua HU Jin Fu ZHANG YING HUA MA Jie JIANG NA YANG Xin Bo LI Zhi Guang YU CHI Jian FEI LI HE GUO   作者單位： Jia Hua HU,YING HUA MA,Jie JIANG,NA YANG,LI HE GUO(Laboratory of Molecular Cell Biology,Institute of Biochemistry and Cell Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai,200031,China)

Jin Fu ZHANG(Department of Urology,Tongji Hospital,Tongji University,389 Xincun Road,Shanghai,200065,China)

Xin Bo LI(New Drug R & D Center,North China Pharmaceutical Group Corporation,388 Heping East Road,Shijia Zhuang,050015,Hebei,China)

Zhi Guang YU CHI(School of life sciences,Fudan University,220 Handan Road,Shanghai, 200433,China)

Jian FEI(Laboratory of Molecular Cell Biology,Institute of Biochemistry and Cell Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai,200031,China;Shanghai Research Center for Biomodel Organism,Shanghai,201203,China) 

刊 名： 細(xì)胞研究(英文版)  ISTIC SCI 英文刊名： CELL RESEARCH  年，卷(期)： 2004 14(1)  分類(lèi)號(hào)： Q2  關(guān)鍵詞： GABA   GAT1   testes   sperm   reproduction   transgenic