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.

产生 Kisspeptins 的 Kiss1 神经元对青春期和生育能力至关重要，但它们的分子调节机制仍未展开。在这里，我们报告在 Kiss1 细胞中对 microRNA 合成酶 Dicer 的先天性消融会导致两种性别的迟发性促性腺激素性性腺功能减退症，但与青春期开始并在婴儿期/少年期保留 Kiss1 神经元群相一致。然而，仅在女性中观察到未能完成青春期和获得生育能力。切丁机的 Kiss1 特异性消融引起青春期过渡期间下丘脑亚群之间Kiss1 细胞数量和Kiss1 /kisspeptin 表达的不同变化，弓状核Kiss1 显着下降水平，与其抑制因子 Mkrn3、Cbx7 和 Eap1 的表达增强有关。我们的数据揭示了 Kiss1 神经元中的 miRNA 生物合成对于青春期的完成和生育能力至关重要，尤其是在女性中，但对于两性的初始生殖成熟和神经元存活都是可有可无的。我们的结果揭示了一个主要的 miRNA 介导的抑制信号抑制程序，这是精确调节Kiss1表达和生殖功能的关键。