MicroRNAs (miRNAs) play important roles in mammalian spermatogenesis, which is highly dependent on Sertoli cells. However, the functions and mechanisms of miRNAs in regulating human Sertoli cells remain largely unknown. Here, we report that hsa-miR-202-3p mediates the proliferation, apoptosis, and synthesis function of human Sertoli cells. miR-202-3p was upregulated in Sertoli cells of Sertoli cell-only syndrome (SCOS) patients compared with obstructive azoospermia (OA) patients with normal spermatogenesis. Overexpression of miR-202-3p induced Sertoli cell apoptosis and inhibited cell proliferation and synthesis, and the effects were opposite when miR-202-3p was knocked down. Lipoprotein receptor-related protein 6 (LRP6) and Cyclin D1 of the Wnt/β-catenin signaling pathway were identified as direct targets of miR-202-3p in Sertoli cells, which were validated by bioinformatics tools and dual-luciferase reporter assay. Differentially expressed LRP6 and Cyclin D1 between OA and SCOS Sertoli cells were also verified. LRP6 small interfering RNA (siRNA) interference not only mimicked the effects of miR-202-3p overexpression, but also antagonized the effects of miR-202-3p inhibition on Sertoli cells. Collectively, miR-202-3p controls the proliferation, apoptosis, and synthesis function of human Sertoli cells via targeting LRP6 and Cyclin D1 of the Wnt/β-catenin signaling pathway. This study thus provides a novel insight into fate determinations of human Sertoli cells and niche of human testis.

微小RNA（miRNA）在哺乳动物精子发生中起重要作用，而精子高度依赖于支持细胞。然而，miRNA在调节人类支持细胞中的功能和机制仍然未知。在这里，我们报道hsa-miR-202-3p介导人类支持细胞的增殖，凋亡和合成功能。与具有正常精子发生的阻塞性无精子症（OA）患者相比，仅Sertoli细胞综合征（SCOS）患者的Sertoli细胞中miR-202-3p上调。miR-202-3p的过表达诱导Sertoli细胞凋亡并抑制细胞增殖和合成，而敲低miR-202-3p的作用则相反。Wnt /β-catenin信号通路的脂蛋白受体相关蛋白6（LRP6）和细胞周期蛋白D1被确定为支持细胞中miR-202-3p的直接靶标，已通过生物信息学工具和双荧光素酶报告基因分析验证。还验证了OA和SCOS支持细胞之间差异表达的LRP6和Cyclin D1。LRP6小干扰RNA（siRNA）干扰不仅模拟了miR-202-3p过表达的作用，而且还拮抗了miR-202-3p抑制作用对支持细胞的作用。miR-202-3p通过靶向Wnt /β-catenin信号通路的LRP6和Cyclin D1共同控制人支持细胞的增殖，凋亡和合成功能。因此，这项研究为人类Sertoli细胞的命运确定和人类睾丸的生境提供了新的见解。LRP6小干扰RNA（siRNA）干扰不仅模拟了miR-202-3p过表达的作用，而且还拮抗了miR-202-3p抑制作用对支持细胞的作用。miR-202-3p通过靶向Wnt /β-catenin信号通路的LRP6和Cyclin D1共同控制人支持细胞的增殖，凋亡和合成功能。因此，这项研究为人类Sertoli细胞的命运确定和人类睾丸的生境提供了新的见解。LRP6小干扰RNA（siRNA）干扰不仅模拟了miR-202-3p过表达的作用，而且还拮抗了miR-202-3p抑制作用对支持细胞的作用。miR-202-3p通过靶向Wnt /β-catenin信号通路的LRP6和Cyclin D1共同控制人支持细胞的增殖，凋亡和合成功能。因此，这项研究为人类Sertoli细胞的命运确定和人类睾丸的生境提供了新的见解。