1. ¹Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
2. ²Department of Urology, Tongji Hospital, Tongji University, 389 Xincun Road, Shanghai 200065, China.
3. ³New Drug R & D Center, North China Pharmaceutical Group Corporation, 388 Heping East Road, Shijia Zhuang 050015, Hebei, China.
4. ⁴School of life sciences, Fudan University, 220 Handan Road, Shanghai 200433, China.
5. ⁵Shanghai Research Center for Biomodel Organism, Shanghai 201203, China.

Correspondence: Dr. Li He GUO, Tel: 0086-21-54921392, Fax: 0086-21-54921391, E-mail: mhzhang@sunm.shcnc.ac.cn.

^*These authors contributed equally to this work.

Received 13 February 2003; Revised 7 August 2003; Accepted 12 August 2003.

Abstract

It is well documented that -aminobutyric acid (GABA) system existed in reproductive organs. Recent researches showed that GABA_A and GABA_B 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.