GABAergic input through GABAB receptors is necessary during a perinatal window to shape gene expression of factors critical to reproduction such as Kiss1.

Lack of GABAB receptors in GABAB1KO mice decreases neonatal ARC Kiss1 expression in females that show impaired reproduction as adults. Here our aim was to selectively impair GABAB signaling during a short postnatal period to evaluate its impact on the reproductive system. Neonatal male and female mice were injected with GABAB antagonist CGP55845 (1 mg/kg BW, sc, CGP) or saline from postnatal day 2 (PND2)-PND6, three times/day (8AM, 1PM, 6PM). One group was killed on PND6 to collect blood samples (hormones by RIA), brains for gene expression in AVPV/PeN and ARC micropunches (qPCR) and gonads for qPCR, hormone contents and histology. A second group of equally treated mice was left to grow. We measured BW along development and parameters of sexual differentiation, puberty onset and estrous cycles. Adult mice were killed: trunk blood (hormones), brains for qPCR and gonads for qPCR and hormone contents were obtained. On PND6 CGP: decreased ARC Kiss1 and increased Tac2 in both sexes; decreased AVPV/PeN Th only in females; increased gonad E2 content in both sexes; decreased LH in females and increased FSH in males; increased ovarian Cyp19a, Esr1 and Esr2; increased primordial and decreased primary and secondary follicles. Neonatally CGP-treated adults showed: decreased ARC Kiss1 and ARC Gnrh1 and increased ARC Gad1 only in males; increased ARC Gabbr1 in both sexes; decreased AVPV/PeN Th only in females; increased LH/FSH ratio in females; increased LH and FSH in males. In conclusion, neonatal GABAergic input through GABAB receptors shapes gene expression of factors critical to reproduction.