Effect of GABA-T on Reproductive Function in Female Rats

Abstract

This study explored the role of γ-aminobutyric acid transaminase (GABA-T) in the puberty and reproductive performance of female rats. Immunofluorescence technique, quantitative real-time PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the distribution of GABA-T and the expression of genes and hormones in female rats, respectively. The results showed that GABA-T was mainly distributed in the arcuate nucleus (ARC), paraventricular nucleus (PVN) and periventricular nucleus (PeN) of the hypothalamus, and in the adenohypophysis, ovarian granulosa cells and oocytes. Abat mRNA level at 28 d was lowest in the hypothalamus and the pituitary; at puberty, it was lowest in the ovary. Abat mRNA level was highest in adults in the hypothalamus; at infancy and puberty, it was highest in the pituitary; and at 21 d it was highest in the ovary. After vigabatrin (GABA-T irreversible inhibitor) was added to hypothalamus cells, the levels of Abat mRNA and Rfrp-3 mRNA were significantly reduced, but Gnrh mRNA increased at the dose of 25 and 50 μg/mL; Kiss1 mRNA was significantly increased but Gabbr1 mRNA was reduced at the 50 μg/mL dose. In prepubertal rats injected with vigabatrin, puberty onset was delayed. Abat mRNA, Kiss1 mRNA and Gnrh mRNA levels were significantly reduced, but Rfrp-3 mRNA level increased in the hypothalamus. Vigabatrin reduced the concentrations of GABA-T, luteinizing hormone (LH) and progesterone (P4), and the ovarian index. Lactation performance was reduced in adult rats with vigabatrin treatment. Four hours after vigabatrin injection, the concentrations of GABA-T and LH were significantly reduced in adult and 25 d rats, but follicle-stimulating hormone (FSH) increased in 25 d rats. In conclusion, GABA-T affects the reproductive function of female rats by regulating the levels of Gnrh, Kiss1 and Rfrp-3 in the hypothalamus as well as the concentrations of LH and P4.

Differentially methylated regions and methylation QTLs for teen depression and early puberty in the Fragile Families Child Wellbeing Study

“…GABA plays a major role in a wide range of brain functions, and its dysfunction due to mutations in ABAT has been linked to many different disorders, including epilepsy, psychomotor difficulties, and Alzheimer’s disease [127]. A study on puberty in goats found ABAT to be one of the implicated genes in methylation changes before and after puberty [121], and this gene was also found to be important in puberty and reproductive functions in rats [95].…”

The expression of IGFBP-5 in the reproductive axis and effect on the onset of puberty in female rats

“…Metestrus, estrus, proestrus, and diestrus are the four stages of the rat estrous cycle [ 20 ]. Progression of the estrous cycle as influenced by the HPG axis is another sign of normal female reproductive development [ 62 ].…”

“…Briefly, 1% sodium pentobarbital solution (60 mg/kg, Sigma, USA) was used to anesthetize rats and deeply positioned in a stereotaxic apparatus. Under aseptic conditions, insert the microsyringe with 2 μl IGFBP-5 protein or saline at a 90° angle into a 2.4 mm posterior to the bregma and 0.5 mm lateral to the midline, 8.6 mm inferior to the skull [ 20 ]. The injection rate was 0.2 μL/min, and the syringe was kept in place for an additional 5 min to allow the injected solution to diffuse into the ARC prior to withdrawal [ 21 ].…”

The Oncogenic Role of γ-Aminobutyrate Aminotransferase in Human Tumor: A Pan-Cancer Analysis

“…Vigabatrin (a small-molecule inhibitor of ABAT) approves for clinical application as an anticonvulsant [15]. Moreover, Vigabatrin has been applied in the study of osteoarthritis and reproduction in mice and has achieved speci c results [16,17]. However, the research progress of ABAT in tumors is insu cient.…”

“…The correlation between ABAT and some tumors, such as PC, BLBC, ACC, AML, and MB, has been demonstrated [7,10,[18][19][20]. In addition, several potential pathways of ABAT have been discovered in different animal studies, such as dogs, zebra sh, and mice [10,17,[21][22][23]. Although there's quite a bit of clinical data, no evidence showed the pan-cancer association between ABAT and different kinds of human tumors.…”