GABAergic input through GABA receptors is necessary during a perinatal window to shape gene expression of factors critical to reproduction such as .

Lack of GABA receptors in GABA knockout mice decreases neonatal ARC kisspeptin 1 () expression in the arcuate nucleus of the hypothalamus (ARC) in females, which show impaired reproduction as adults. Our aim was to selectively impair GABA signaling during a short postnatal period to evaluate its impact on the reproductive system. Neonatal male and female mice were injected with the GABA antagonist CGP 55845 (CGP, 1 mg/kg body wt sc) or saline from postnatal () to , three times per day (8 AM, 1 PM, and 6 PM). One group was killed on for collection of blood samples (hormones by radioimmunoassay), brains for gene expression in the anteroventral periventricular nucleus-periventricular nucleus continuum (AVPV/PeN), and ARC micropunches [quantitative PCR (qPCR)] and gonads for qPCR, hormone contents, and histology. A second group of mice was injected with CGP (1 mg/kg body wt sc) or saline from to , three times per day (8 AM, 1 PM, and 6 PM), and left to grow to adulthood. We measured body weight during development and parameters of sexual differentiation, puberty onset, and estrous cycles. Adult mice were killed, and trunk blood (hormones), brains for qPCR, and gonads for qPCR and hormone contents were obtained. Our most important findings on include the CGP-induced decrease in ARC and increase in neurokinin B () in both sexes; the decrease in AVPV/PeN tyrosine hydroxylase () only in females; the increase in gonad estradiol content in both sexes; and the increase in primordial follicles and decrease in primary and secondary follicles. Neonatally CGP-treated adults showed decreased ARC and ARC gonadotropin-releasing hormone () and increased ARC glutamic acid decarboxylase 67 () only in males; increased ARC GABA receptor subunit 1 () in both sexes; and decreased AVPV/PeN only in females. We demonstrate that ARC expression is chronically downregulated in males and that the normal sex difference in AVPV/PeN expression is abolished. In conclusion, neonatal GABAergic input through GABA receptors shapes gene expression of factors critical to reproduction.