RT Journal Article
T1 Dicer ablation in Kiss1 neurons impairs puberty and fertility preferentially in female mice.
A1 Roa, Juan
A1 Ruiz-Cruz, Miguel
A1 Ruiz-Pino, Francisco
A1 Onieva, Rocio
A1 Vazquez, Maria J
A1 Sanchez-Tapia, Maria J
A1 Ruiz-Rodriguez, Jose M
A1 Sobrino, Veronica
A1 Barroso, Alexia
A1 Heras, Violeta
A1 Velasco, Inmaculada
A1 Perdices-Lopez, Cecilia
A1 Ohlsson, Claes
A1 Avendaño, Maria Soledad
A1 Prevot, Vincent
A1 Poutanen, Matti
A1 Pinilla, Leonor
A1 Gaytan, Francisco
A1 Tena-Sempere, Manuel
K1 DEAD-box RNA helicases
K1 Fertility
K1 Kisspeptins
K1 MicroRNAs
AB Kiss1 neurons, producing kisspeptins, are essential for puberty and fertility, but their molecular regulatory mechanisms remain unfolded. Here, we report that congenital ablation of the microRNA-synthesizing enzyme, Dicer, in Kiss1 cells, causes late-onset hypogonadotropic hypogonadism in both sexes, but is compatible with pubertal initiation and preserved Kiss1 neuronal populations at the infantile/juvenile period. Yet, failure to complete puberty and attain fertility is observed only in females. Kiss1-specific ablation of Dicer evokes disparate changes of Kiss1-cell numbers and Kiss1/kisspeptin expression between hypothalamic subpopulations during the pubertal-transition, with a predominant decline in arcuate-nucleus Kiss1 levels, linked to enhanced expression of its repressors, Mkrn3, Cbx7 and Eap1. Our data unveil that miRNA-biosynthesis in Kiss1 neurons is essential for pubertal completion and fertility, especially in females, but dispensable for initial reproductive maturation and neuronal survival in both sexes. Our results disclose a predominant miRNA-mediated inhibitory program of repressive signals that is key for precise regulation of Kiss1 expression and, thereby, reproductive function.
PB Nature Publishing Group
YR 2022
FD 2022-07-26
LK http://hdl.handle.net/10668/19541
UL http://hdl.handle.net/10668/19541
LA en
NO Roa J, Ruiz-Cruz M, Ruiz-Pino F, Onieva R, Vazquez MJ, Sanchez-Tapia MJ, et al.  Dicer ablation in Kiss1 neurons impairs puberty and fertility preferentially in female mice. Nat Commun. 2022 Aug 9;13(1):4663
NO This work was supported by grants BFU2014-57581-P, BFU2017-83934-P, and PID2020-118660GB-I00 (to M.T.-S.—Ministerio de Economía yCompetitividad, Spain; co-funded with EU funds from FEDER Program);Project PIE-00005 (to M.T.-S) and grants PI16/01243 and PI19/00257(to J.R.—Instituto de Salud Carlos III, Ministerio de Sanidad, Spain; cofunded with EU funds from FEDER Program); Project P12-FQM-01943(to M.T.-S.—Junta de Andalucía, Spain); Project REP-655232(ReprObesity; to M.T.-S.–European Union); and COST Action BM1105(to M.T.-S. and V.P.–European Union). CIBER Fisiopatología de laObesidad y Nutrición is an initiative of Instituto de Salud Carlos III,Spain. The authors are indebted to Dr. Esther Peralbo, Head of theCytometry Unit of IMIBIC, for her superb assistance in the optimizationand implementation of protocols of FACS for Kiss1 neuronal isolation.The assistance of Profs. Catherine Dulac and Robert A. Steiner forproviding the parental Kiss1Cre/− and GnRH-Crepos mouse lines is cordially appreciated.
DS RISalud
RD May 9, 2025