Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Obstetrics and Gynecology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China.
J Obstet Gynaecol. 2023 Dec;43(2):2237574. doi: 10.1080/01443615.2023.2237574.
Circular RNAs are involved in the pathogenesis of various diseases, although its expression pattern and role in polycystic ovary syndrome (PCOS), characterised by hyperandrogenism, are not very clear. This article assessed the circRNAs expression profile in the ovaries of PCOS mice by circRNAs high-throughput sequencing and explored the role of circEpha5 in hyperandrogenism. The results showed that the overexpression of circEpha5 in mouse preantral follicles could increase the expression of , an androgen synthesis-related gene, which resulted in a higher serum level of testosterone. Dual-luciferase reporter gene studies identified miR-758-5p as a direct target of circEpha5. Consequently, miR-758-5p expression was downregulated upon circEpha5 overexpression. Ectopically expressed miR-758-5p reversed the stimulation effects of circEpha5 on steroidogenesis-related gene expression and testosterone release. Therefore, circEpha5 could sponge miR-758-5p to regulate the expression of , thereby promoting the synthesis and secretion of androgen in the preantral follicles. This work is contributed to the understanding of the pathogenesis of hyperandrogenemia and lays the foundation for the development of therapeutic targets of PCOS hyperandrogenism.
环状 RNA 参与多种疾病的发病机制，尽管其在多囊卵巢综合征（PCOS）中的表达模式及其作用尚不清楚，PCOS 的特征是高雄激素血症。本文通过环状 RNA 高通量测序评估了 PCOS 小鼠卵巢中的 circRNAs 表达谱，并探讨了 circEpha5 在高雄激素血症中的作用。结果表明，circEpha5 在小鼠原始卵泡中的过表达可以增加雄激素合成相关基因的表达，导致血清睾酮水平升高。双荧光素酶报告基因研究鉴定出 miR-758-5p 是 circEpha5 的直接靶基因。因此，circEpha5 过表达下调了 miR-758-5p 的表达。外源性表达 miR-758-5p 逆转了 circEpha5 对类固醇生成相关基因表达和睾酮释放的刺激作用。因此，circEpha5 可以通过海绵吸附 miR-758-5p 来调节基因的表达，从而促进原始卵泡中雄激素的合成和分泌。这项工作有助于理解高雄激素血症的发病机制，并为 PCOS 高雄激素血症的治疗靶点的开发奠定了基础。
