Inhibition of GABAB signaling in female neonates alters ovary gene expression and delays puberty onset.

BIZZOZZERO MARIANNE; LUX LANTOS V; LIBERTUN CARLOS; DI GIORGIO NOELIA P

Congreso; XX Jornadas anuales de la Sociedad Argentina de Biologia y la XVII Jornada de la Sociedad Uruguaya de Biociencias.; 2018

INHIBITION OF GABAB SIGNALING IN FEMALE NEONATES ALTERS OVARY GENE EXPRESSION AND DELAYS PUBERTY ONSET.Bizzozzero Hiriart M, Di Giorgio NP, Libertun C and Lux-Lantos V. Instituto de Biología y Medicina Experimental (IBYME-CONICET, Buenos Aires, Argentina). m.bizzozzero@hotmail.comGABAB antagonist (CGP55845, CGP) administration to neonatal BALB/C mice significantly decreased ARC Kiss1 expression in both sexes. Cyp19a1, Esr1/2, Pgr hypothalamic expression were not affected by this treatment. Nevertheless, ovarian and testicular E2 contents were significantly increased in CGP-treated mice. Here we analyzed the impact of neonatal CGP administration on PND6 ovarian gene expression and ovarian morphology and the effect on body weight (BW), sexual differentiation, puberty onset, and adult hormone levels and estrous cyclicity. Female Balb/c mice were injected with CGP (1 mg/kg, sc) or saline from postnatal day 2 (PND2) to PND6±1, three times/day (8AM, 1PM, 6PM). One set of mice was sacrificed at 3PM (after two injections on the last day). One ovary was collected to determine aromatase (Cyp19a1), estrogen receptors (Esr1/2), kisspeptin (Kiss1) and kisspeptin receptor (Kiss1r) gene expression by qPCR; the other ovary was used to analyze ovarian morphology. In the second set of animals, equally treated, BW and anogenital index (AGI=ano-genital distance (AGD)/BW) were evaluated on PND7, PND14 and PND21 and puberty onset was determined by vaginal opening (VO). In adulthood, LH and FSH levels were determined by RIA and estrous cycles were evaluated.CGP increased Cyp19a1, Esr1 and Esr2 expression in neonatal ovaries (Cyp19a1: CTRL:0.97±0.32 vs CGP:2.5±0.55: p