Blocking GABAB receptors (GABABR) from birth to weaning induces profound changes in the gonadotropic axis in adult mice

BIZZOZZERO HIRIART, MARIANNE; DI GIORGIO N; REPETTO, M; LIBERTUN, C; LUX LANTOS V

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias; 2020

SAB

BLOCKING GABAB RECEPTORS (GABABR) FROM BIRTH TO WEANING INDUCES PROFOUND CHANGES IN THE GONADOTROPIC AXIS IN ADULT MICEBizzozzero Hiriart M, Di Giorgio NP, Repetto E, Libertun C and Lux-Lantos V. Instituto de Biología y Medicina Experimental (IBYME-CONICET, Buenos Aires, Argentina). m.bizzozzero@hotmail.comWe have previously shown that administration of GABAB antagonist (CGP55845) to neonatal mice from postnatal day (PND) 2 to weaning (PND21) significantly decreased arcuate nucleus (ARC) kisspeptin (Kiss1) expression and increased dynorphin (Pdyn) expression in both sexes on PND21. Here our aim was to evaluate the effect of this sustained inhibition of GABABR signaling on the gonadotropic axis in adulthood.Neonatal Balb/c males (M) and females (F) were injected with CGP55845 (1 mg/kg, sc, CGP) or saline from PND2-21, three times/day (8AM, 1PM, 6PM) and sacrificed in adulthood. Serum samples and gonads were collected for hormonal measurements (RIA). Brains were frozen and 500 µm slices were obtained on a cryostat. ARC and anteroventral periventricular nucleus (AVPV) micropunches were obtained. Kiss1, Pdyn, neurokinin B (Tac2), tyrosine hydrolxylase (Th), progesterone receptor (Pgr) and GnRH (Gnrh1) mRNA expression was assessed in the micropunches by qPCR. Body weight (BW) and AGI (anogenital distance/BW) were evaluated on PND7, 14 and 21. Puberty onset was determined by vaginal opening (VO) or preputial separation (PS).CGP significantly increased BW on PND21 in F (p