BACKGROUND/AIMS: Adult mice lacking functional GABAB receptors (GABAB1KO) show altered Gnrh1 and Gad1 expressions in the preoptic area-anterior hypothalamus (POA-AH) and females display disruption of cyclicity and fertility. Here we addressed whether sexual differentiation of the brain and the proper wiring of the GnRH and kisspeptin systems were already disturbed in postnatal day 4 (PND4) GABAB1KO mice. METHODS: PND4 wild-type (WT) and GABAB1KO mice of both sexes were sacrificed; tissues were collected to determine mRNA expression (qPCR), amino acids (HPLC), and hormones (RIA and/or IHC). RESULTS: GnRH neuron number (IHC) did not differ among groups in olfactory bulbs or OVLT-POA. Gnrh1 mRNA (qPCR) in POA-AH was similar among groups. Gnrh1 mRNA in medial basal hypothalamus (MBH) was similar in WTs but was increased in GABAB1KO females compared to GABAB1KO males. Hypothalamic GnRH (RIA) was sexually different in WTs (males > females), but this sex difference was lost in GABAB1KOs; the same pattern was observed when analyzing only the MBH, but not in the POA-AH. Arcuate nucleus Kiss1 mRNA (micropunch-qPCR) was higher in WT females than in WT males and GABAB1KO females. Gad1 mRNA in MBH was increased in GABAB1KO females compared to GABAB1KO males. Serum LH and gonadal estradiol content were also increased in GABAB1KOs. CONCLUSION: We demonstrate that GABABRs participate in the sexual differentiation of the ARC/MBH, because sex differences in several reproductive genes, such as Gad1, Kiss1 and Gnrh1, are critically disturbed in GABAB1KO mice at PND4, probably altering the organization and development of neural circuits governing the reproductive axis.
BACKGROUND/AIMS: Adult mice lacking functional GABAB receptors (GABAB1KO) show altered Gnrh1 and Gad1 expressions in the preoptic area-anterior hypothalamus (POA-AH) and females display disruption of cyclicity and fertility. Here we addressed whether sexual differentiation of the brain and the proper wiring of the GnRH and kisspeptin systems were already disturbed in postnatal day 4 (PND4) GABAB1KO mice. METHODS: PND4 wild-type (WT) and GABAB1KO mice of both sexes were sacrificed; tissues were collected to determine mRNA expression (qPCR), amino acids (HPLC), and hormones (RIA and/or IHC). RESULTS:GnRH neuron number (IHC) did not differ among groups in olfactory bulbs or OVLT-POA. Gnrh1 mRNA (qPCR) in POA-AH was similar among groups. Gnrh1 mRNA in medial basal hypothalamus (MBH) was similar in WTs but was increased in GABAB1KO females compared to GABAB1KO males. Hypothalamic GnRH (RIA) was sexually different in WTs (males > females), but this sex difference was lost in GABAB1KOs; the same pattern was observed when analyzing only the MBH, but not in the POA-AH. Arcuate nucleus Kiss1 mRNA (micropunch-qPCR) was higher in WT females than in WT males and GABAB1KO females. Gad1 mRNA in MBH was increased in GABAB1KO females compared to GABAB1KO males. Serum LH and gonadal estradiol content were also increased in GABAB1KOs. CONCLUSION: We demonstrate that GABABRs participate in the sexual differentiation of the ARC/MBH, because sex differences in several reproductive genes, such as Gad1, Kiss1 and Gnrh1, are critically disturbed in GABAB1KO mice at PND4, probably altering the organization and development of neural circuits governing the reproductive axis.
Authors: Daniel J Haisenleder; Aleisha H Schoenfelder; Elizabeth S Marcinko; Lisa M Geddis; John C Marshall Journal: Endocrinology Date: 2011-09-20 Impact factor: 4.736
Authors: Leonor Pinilla; Enrique Aguilar; Carlos Dieguez; Robert P Millar; Manuel Tena-Sempere Journal: Physiol Rev Date: 2012-07 Impact factor: 37.312
Authors: Paolo N Catalano; María Marta Bonaventura; Patricia Silveyra; Bernhard Bettler; Carlos Libertun; Victoria A Lux-Lantos Journal: Neuroendocrinology Date: 2005 Impact factor: 4.914
Authors: Margaret E Wierman; John E Pawlowski; Melissa P Allen; Mei Xu; Daniel A Linseman; Sheila Nielsen-Preiss Journal: Trends Endocrinol Metab Date: 2004-04 Impact factor: 12.015
Authors: Pablo Ignacio Felipe Inserra; Santiago Elías Charif; Noelia Paula Di Giorgio; Lucía Saucedo; Alejandro Raúl Schmidt; Nicolas Fraunhoffer; Julia Halperin; María Constanza Gariboldi; Noelia Paola Leopardo; Victoria Lux-Lantos; Candela Rocío Gonzalez; Alfredo Daniel Vitullo; Verónica Berta Dorfman Journal: J Mol Histol Date: 2017-03-19 Impact factor: 2.611
Authors: Santiago Elías Charif; Pablo Ignacio Felipe Inserra; Alejandro Raúl Schmidt; Santiago Andrés Cortasa; Sofía Proietto; María Clara Corso; Julia Halperin; Noelia Paula Di Giorgio; Victoria Lux-Lantos; Alfredo Daniel Vitullo; Verónica Berta Dorfman Journal: J Comp Physiol B Date: 2021-08-30 Impact factor: 2.200
Authors: Shannon B Z Stephens; Noelia P Di Giorgio; Reanna B Liaw; Ruby A Parra; Jennifer A Yang; Navdeep Chahal; Victoria A Lux-Lantos; Alexander S Kauffman Journal: Endocrinology Date: 2018-09-01 Impact factor: 4.736
Authors: Pedro Javier Torres; Eugenia Mercedes Luque; Noelia Paula Di Giorgio; Nicolás David Ramírez; Marina Flavia Ponzio; Verónica Cantarelli; Valeria Paola Carlini; Victoria Lux-Lantos; Ana Carolina Martini Journal: Reprod Sci Date: 2021-04-15 Impact factor: 3.060
Authors: Santiago E Charif; Pablo I F Inserra; Alejandro R Schmidt; Noelia P Di Giorgio; Santiago A Cortasa; Candela R Gonzalez; Victoria Lux-Lantos; Julia Halperin; Alfredo Daniel Vitullo; Verónica B Dorfman Journal: Physiol Rep Date: 2017-10-16