Ma Jie, Lin Yingying, Xiong Wei, Liu Xiaoxue, Pan Minghui, Sun Jiazeng, Sun Yanan, Li Yixuan, Guo Huiyuan, Pang Guofang, Wang Xiaoyu, Ren Fazheng
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China.
Int J Mol Sci. 2024 Dec 5;25(23):13089. doi: 10.3390/ijms252313089.
Male-typical behaviors such as aggression and mating, which reflect sexual libido in male mice, are regulated by the hypothalamus, a crucial part of the nervous system. Previous studies have demonstrated that microRNAs (miRNAs), especially , play a vital role in reproduction and the neural control of behaviors. However, it remains unclear whether affects reproduction through the hypothalamus-mediated regulation of male-typical behaviors. Here, we constructed two mouse knockout models by ablating either the or cluster. Compared to WT, the ablation of in male mice significantly reduced the incidence of aggression by 60% and the incidence of mating by 46.15%. Furthermore, the loss of in male mice led to the downregulation of androgen receptor (AR) in the ventromedial hypothalamus. Transcriptomic analysis of the hypothalamus of -deficient mice revealed inflammatory activation and aberrant expression of genes associated with male-typical behaviors, including , , , and . Using bioinformatics analysis and dual-luciferase reporter assays, we identified zinc finger protein 36 () as a direct downstream target gene of . We subsequently showed that ZFP36 colocalized with AR in GT1-7 cells. Furthermore, inhibition of or in GT1-7 cells led to an increase in AR expression. Collectively, our results demonstrate that the axis in the hypothalamus plays a pivotal role in the regulation of aggression and mating in male mice, providing a potential therapeutic target for treating infertility caused by low libido.
诸如攻击和交配等典型的雄性行为反映了雄性小鼠的性本能，这些行为由下丘脑调节，下丘脑是神经系统的关键部分。先前的研究表明，微小RNA（miRNA），尤其是 ，在生殖和行为的神经控制中起着至关重要的作用。然而， 是否通过下丘脑介导的典型雄性行为调节来影响生殖仍不清楚。在这里，我们通过切除 或 簇构建了两种小鼠基因敲除模型。与野生型相比，雄性小鼠中 的缺失显著降低了60%的攻击发生率和46.15%的交配发生率。此外，雄性小鼠中 的缺失导致腹内侧下丘脑雄激素受体（AR）的下调。对 缺陷小鼠下丘脑的转录组分析揭示了与典型雄性行为相关的基因的炎症激活和异常表达，包括 、 、 和 。通过生物信息学分析和双荧光素酶报告基因检测，我们确定锌指蛋白36（ ）是 的直接下游靶基因。我们随后表明，ZFP36在GT1-7细胞中与AR共定位。此外，在GT1-7细胞中抑制 或 导致AR表达增加。总的来说，我们的结果表明，下丘脑的 轴在雄性小鼠攻击和交配的调节中起关键作用，为治疗性欲低下引起的不孕症提供了一个潜在的治疗靶点。
