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

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Date

2022-07-26

Authors

Roa, Juan
Ruiz-Cruz, Miguel
Ruiz-Pino, Francisco
Onieva, Rocio
Vazquez, Maria J
Sanchez-Tapia, Maria J
Ruiz-Rodriguez, Jose M
Sobrino, Veronica
Barroso, Alexia
Heras, Violeta

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Nature Publishing Group
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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.

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MeSH Terms

Animals
Female
Male
Mice
Neurons
Ribonuclease III
Sexual maturation

DeCS Terms

Maduración sexual
Masculino
Neuronas
Ratones
Ribonucleasa III

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Keywords

DEAD-box RNA helicases, Fertility, Kisspeptins, MicroRNAs

Citation

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