Abstract
Simple SummaryThis study evaluated the effect of γ-aminobutyric acid transaminase (GABA-T) on reproduction in female rats. Our results showed that GABA-T expressed in the reproductive axis of female rats at different developmental stages, and inhibiting GABA-T affected Rfrp-3, Gnrh and Kiss1 mRNA transcription levels in hypothalamic and reduced the concentration of GABA-T, LH, and P4 in serum. At the same time, the initiation of the puberty was delayed, and led to disordered estrous cycle and reduced breastfeeding performance in adult female rats. This study showed that 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.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.
Highlights
Reproduction is the process by which an animal breeds and produces offspring
In the hypothalamus (Figure 1A), Abat mRNA level was significantly reduced at infancy, 28 d, puberty (p < 0.01) and 21 d (p < 0.05) rats compared with adults; the level of Abat mRNA at infancy and 28 d were significantly lower than that at 21 d and puberty (p < 0.01)
In the pituitary (Figure 1B), the level of Abat mRNA was the lowest at 28 d, which was significantly lower than that at infancy, 21 d, puberty and adult (p < 0.01); there was no significant difference in the expression of Abat mRNA between infancy and puberty (p > 0.05), but, compared with these two periods, the expression of Abat mRNA was significantly reduced at 21 d and adult stages (p < 0.01)
Summary
Reproduction is the process by which an animal breeds and produces offspring. Puberty is essential in the growth and development of animals, and is an important symbol of reproductive ability [1].After the onset of puberty, the reproductive organs become mature and begin to perform reproductive activities. Puberty is essential in the growth and development of animals, and is an important symbol of reproductive ability [1]. The onset of puberty is regulated by the hypothalamic–pituitary–gonadal axis (HPGA) [2]. The increase in gonadotropin-releasing hormone (GnRH) released in the hypothalamus before puberty results in the increased release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the anterior pituitary; both hormones act on the gonad, stimulating their development, gametogenesis and sexual steroid production [3]. Many factors can affect animal puberty and reproduction. The system of kisspeptin-G protein-coupled receptor 54 (kiss1-GPR54) [4], γ-aminobutyric acid (GABA) [5], leptin [6], D-Aspartate [7] and others are essential in regulating reproduction. The receptor GPR147 of RFRP-3 is expressed in the subsets of GnRH and kisspeptin neurons, which can inhibit kisspeptin neurons and
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