Vesicular GABA transport expression in kisspeptin cells may contribute to the preovulatory gonadotropin surge.

Abstract

Background: The neurotransmitter gamma-aminobutyric acid (GABA) plays a vital role in the modulation of reproductive function by controlling gonadotropin-releasing hormone (GnRH) secretion. Most kisspeptin neurons, which are key regulators of GnRH neurons, coexpress GABA and other neuropeptides. However, whether the expression of the vesicular GABA transporter (Vgat) in kisspeptin cells contributes to the reproductive phenotype of mice remains unclear.

Methods: Brain slices from female vesicular GABA transporter-Cre/GFP (Vgat-Cre/GFP) mice were used to assess GABAergic coexpression in kisspeptin neurons during diestrus and proestrus. Mice carrying conditional ablation of Slc32a1 (referred to as Vgat) in Kiss1-expressing cells (Kiss1-Cre/Vgat ^flox/flox mice) were generated to study possible effects on reproduction and metabolism.

Results: 50-60% of kisspeptin neurons in the anteroventral periventricular and rostral periventricular nuclei are GABAergic. However, the percentage of GABAergic kisspeptin neurons did not differ between proestrus and diestrus stages. Deletion of Vgat in kisspeptin cells was sufficient to downregulate Gnrh1 and Kiss1r expression in the rostral periventricular region of female mice. In contrast, Cartpt mRNA expression in the mediobasal hypothalamus was downregulated only in male mice compared with controls. Body composition, puberty onset, and fertility were preserved in both sexes; however, female Kiss1-Cre/Vgat ^flox/flox mice exhibited significantly lower serum luteinizing hormone levels at proestrus.

Discussion: These findings indicate that Vgat expression in kisspeptin neurons may contribute to LH surge generation but is not essential for the onset of puberty or for the maintenance of fertility in either female or male mice.