Impaired reproduction in transgenic mice overexpressing Gamma-aminobutyric acid transporter I (GAT1).
It is well documented that g-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.
Hu
Jia Hua
JH
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Zhang
Jin Fu
JF
Ma
Ying Hua
YH
Jiang
Jie
J
Yang
Na
N
Li
Xin Bo
XB
Yu Chi
Zhi Guang
ZG
Fei
Jian
J
Guo
Li He
LH
D000818:Animals; D001947:Breeding; D005260:Female; D005298:Fertility / Q000235:genetics; D050485:GABA Plasma Membrane Transport Proteins; D015870:Gene Expression / Q000235:genetics*; D007985:Leydig Cells / Q000378:metabolism / Q000473:pathology; D008098:Litter Size / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000254:growth & development*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D011944:Receptors, Androgen / Q000235:genetics / Q000502:physiology; D012098:Reproduction / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012671:Seminiferous Tubules / Q000378:metabolism / Q000473:pathology; D013091:Spermatogenesis / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000737:chemistry / Q000254:growth & development / Q000473:pathology; D013739:Testosterone / Q000097:blood
D050485:GABA Plasma Membrane Transport Proteins; D026901:Membrane Transport Proteins; D011944:Receptors, Androgen; C493414:Slc6a1 protein, mouse; D013739:Testosterone; D012313:RNA