Dicer ablation in Kiss1 neurons impairs puberty and fertility preferentially in female mice

Juan Roa (), Miguel Ruiz-Cruz, Francisco Ruiz-Pino, Rocio Onieva, Maria J. Vazquez, Maria J. Sanchez-Tapia, Jose M. Ruiz-Rodriguez, Veronica Sobrino, Alexia Barroso, Violeta Heras, Inmaculada Velasco, Cecilia Perdices-Lopez, Claes Ohlsson, Maria Soledad Avendaño, Vincent Prevot, Matti Poutanen, Leonor Pinilla, Francisco Gaytan and Manuel Tena-Sempere ()
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Juan Roa: Instituto Maimónides de Investigación Biomédica de Córdoba
Miguel Ruiz-Cruz: Instituto Maimónides de Investigación Biomédica de Córdoba
Francisco Ruiz-Pino: Instituto Maimónides de Investigación Biomédica de Córdoba
Rocio Onieva: Instituto Maimónides de Investigación Biomédica de Córdoba
Maria J. Vazquez: Instituto Maimónides de Investigación Biomédica de Córdoba
Maria J. Sanchez-Tapia: Instituto Maimónides de Investigación Biomédica de Córdoba
Jose M. Ruiz-Rodriguez: Instituto Maimónides de Investigación Biomédica de Córdoba
Veronica Sobrino: Instituto Maimónides de Investigación Biomédica de Córdoba
Alexia Barroso: Instituto Maimónides de Investigación Biomédica de Córdoba
Violeta Heras: Instituto Maimónides de Investigación Biomédica de Córdoba
Inmaculada Velasco: Instituto Maimónides de Investigación Biomédica de Córdoba
Cecilia Perdices-Lopez: Instituto Maimónides de Investigación Biomédica de Córdoba
Claes Ohlsson: Sahlgrenska Academy, University of Gothenburg
Maria Soledad Avendaño: Instituto Maimónides de Investigación Biomédica de Córdoba
Vincent Prevot: Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition
Matti Poutanen: Sahlgrenska Academy, University of Gothenburg
Leonor Pinilla: Instituto Maimónides de Investigación Biomédica de Córdoba
Francisco Gaytan: Instituto Maimónides de Investigación Biomédica de Córdoba
Manuel Tena-Sempere: Instituto Maimónides de Investigación Biomédica de Córdoba

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32347-4

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DOI: 10.1038/s41467-022-32347-4

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