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Updated: Jul 19, 2025
Author Spotlight: Investigating the Mechanisms and Inducing Models of Polycystic Ovary Syndrome
Published on: July 5, 2024
CircEpha5 regulates the synthesis and secretion of androgen in mouse preantral follicles by targeting miR-758-5p
Xueying Zhang1,2, Jiaxuan Liu3, Hao Wu3
1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Abstract:
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 Cyp17a1, 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 Cyp17a1, 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.
Insights
Circular RNA circEpha5 promotes androgen synthesis in polycystic ovary syndrome (PCOS) by sponging miR-758-5p, increasing testosterone levels. This finding offers potential therapeutic targets for PCOS hyperandrogenism.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are implicated in disease pathogenesis, but their role in polycystic ovary syndrome (PCOS) remains unclear.
- PCOS is characterized by hyperandrogenism, a condition involving excessive androgen production.
Purpose of the Study:
- To investigate the circRNA expression profile in the ovaries of PCOS mice.
- To explore the specific role of circEpha5 in the development of hyperandrogenism in PCOS.
Main Methods:
- CircRNA high-throughput sequencing was employed to analyze ovarian circRNA expression in PCOS mice.
- Overexpression of circEpha5 in mouse preantral follicles and dual-luciferase reporter gene assays were used to determine molecular mechanisms.
Main Results:
- Overexpression of circEpha5 increased Cyp17a1 expression and serum testosterone levels in mouse models.
- miR-758-5p was identified as a direct target of circEpha5, with its expression downregulated upon circEpha5 overexpression.
- Ectopic expression of miR-758-5p counteracted the effects of circEpha5 on steroidogenesis and testosterone release.
Conclusions:
- circEpha5 acts as a molecular sponge for miR-758-5p, regulating Cyp17a1 expression and promoting androgen synthesis in preantral follicles.
- This mechanism contributes to hyperandrogenism in PCOS and suggests circEpha5 as a potential therapeutic target.
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