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Updated: Sep 17, 2025
A Hyperandrogenic Mouse Model to Study Polycystic Ovary Syndrome
Published on: October 2, 2018
miR-423-3p inhibits CTNNBIP1/WNT preventing hyperandrogenic polycystic ovary syndrome†
Shanshan Zhang1,2, Yajing Liu3, Mingming Wang4,5
1School of Life Sciences, Jining Medical University, No. 669 Xueyuan Road, Donggang District, Rizhao, Shandong Province 276826, PR China.
Abstract:
Polycystic ovary syndrome (PCOS) lacks the generally accepted diagnostic biomarkers and targeted therapy. Increasing evidence indicates that microRNAs play a crucial role in PCOS. Hereby, we tested the functional implications of a novel MicroRNA (miR-423-3p) as a mediator in the progress of hyperandrogenic PCOS, as well as its potential as a new serum biomarker and therapeutic target for the PCOS. We found significantly decreased miR-423-3p levels in serum, human granulosa cells (hGCs), and follicular fluid of PCOS patients (n = 40) compared to healthy controls (n = 30), and this decrease corroborated in PCOS-like mouse models. The receiver operating characteristic curve analysis for circulating miR-423-3p indicated high diagnostic potential as a biomarker, with an area under the curve of 82%. miR-423-3p influenced hGC (Human ovarian granulosa cell line KGN) proliferation by directly targeting CTNNBIP1-modulated Wingless-type (WNT) signaling pathway. We further proved as mechanistic role that the elevated dihydrotestosterone inhibited the expression of miR-423-3p via the activation of the androgen receptor, and the overexpression of miR-423-3p normalized the function of androgen-induced GCs. While we overexpressed miR-423-3p, it counteracted androgen-induced dysfunction in GCs. Antiandrogen treatment restored the reproductive phenotypes in letrozole-induced PCOS-like mice and regulated miR-423-3p expression and its downstream effects. Ovarian intrabursal injection of miR-423-3p antagomir in wild-type mice induced PCOS-like phenotypes, further underscoring its functional role. Our results demonstrated that miR-423-3p emerged as a novel mediator in hyperandrogenic PCOS progression, and it holds promise as both a diagnostic biomarker and a therapeutic target.
Insights
Polycystic ovary syndrome (PCOS) lacks diagnostic biomarkers. This study identifies miR-423-3p as a potential biomarker and therapeutic target, showing its decreased levels in PCOS patients and its role in hyperandrogenism.
Area of Science:
- Endocrinology and Reproductive Biology
- Molecular Biology and Genetics
Background:
- Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology.
- PCOS lacks universally accepted diagnostic biomarkers and effective targeted therapies, necessitating research into novel molecular mechanisms and potential therapeutic targets.
Purpose of the Study:
- To investigate the functional role of microRNA-423-3p (miR-423-3p) in the pathogenesis of hyperandrogenic PCOS.
- To evaluate the potential of miR-423-3p as a diagnostic biomarker and therapeutic target for PCOS.
Main Methods:
- Quantification of miR-423-3p levels in serum, granulosa cells, and follicular fluid from PCOS patients and healthy controls.
- In vitro studies using human granulosa cells (KGN) to assess the effect of miR-423-3p on proliferation and WNT signaling.
- In vivo studies using PCOS-like mouse models to investigate the therapeutic potential of modulating miR-423-3p levels and the effect of antiandrogen treatment.
Main Results:
- Significantly decreased miR-423-3p levels were observed in serum, granulosa cells, and follicular fluid of PCOS patients compared to controls.
- Receiver operating characteristic (ROC) curve analysis indicated a high diagnostic potential for circulating miR-423-3p (AUC of 82%).
- miR-423-3p directly targets CTNNBIP1, modulating the WNT signaling pathway and influencing KGN cell proliferation. Elevated dihydrotestosterone (DHT) inhibits miR-423-3p expression via androgen receptor activation, while miR-423-3p overexpression counteracts DHT-induced granulosa cell dysfunction.
Conclusions:
- miR-423-3p is a novel mediator in the progression of hyperandrogenic PCOS.
- miR-423-3p demonstrates significant promise as a diagnostic biomarker for PCOS.
- Modulating miR-423-3p levels represents a potential therapeutic strategy for PCOS.
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