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

Abstract

It is well documented that γ-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.

Expression of GAT1 in Male Reproductive System and its Effects on Reproduction in Mice

“…2000]. Our previous studies revealed abnormal testis morphology in adult male TG mice [Ma et al 2000;Hu et al 2004]. The present study confirmed that GABA transport protein GAT1 was present in WT testes, epididymis, and sperm.…”

“…These findings suggested that GABA and its receptors were important components of the reproductive system. The presence of GAT1 has been confirmed in rat and mouse testes and sperm [Ma et al 2000;Hu et al 2004]. In the present study, WT mice and GAT1 overexpressing TG mice were used to confirm the existence and define the location of GAT1 in the reproductive system of male mice, including testis, epididymis, and sperm.…”

“…GAT1-overexpressed transgenic mice and their littermates were provided by the Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences [Hu et al 2004]. TG referred to homozygote of GAT1 transgene and WT (wild-type) referred to the littermates of TG without GAT1 transgene.…”

Differential Distribution of GABA and GAT1 in Mouse Epididymis

“…However, there are no remarkable changes in the epididymis [15]. This can explain that the male reproduction is compromised in GAT1 transgenic mice [15,16]. In the current study, we found that GABA and GAT1 distributed differentially in mouse epididymis caput, corpus, and cauda.…”

“…Thus GABA may be a physiological regulator of sperm function. GAT1 is also observed in testes, epididymis and sperms [13][14][15][16][17][18]. The function of GAT1 has been demonstrated, showing compromised reproductive capacity in the GAT1 transgenic mice.…”