Metformin improves polycystic ovary syndrome through the regulation of granulosa cell proliferation and apoptosis via the miR-103a-3p/PTEN signaling pathway.

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, often characterized by polycystic ovarian, hyperandrogenism, and menstrual irregularities, which can lead to infertility and other metabolic issues. The mechanisms underlying these symptoms remain complex, with granulosa cells proliferation and apoptosis playing a key role in the pathogenesis of PCOS. In this study, we investigate the potential of metformin to regulate the miR-103a-3p/PTEN signaling pathway in granulosa cells, which may help address these dysfunctions. We first created an in vitro PCOS model using KGN cells treated with testosterone propionate (TP) and tested the effects of metformin alongside miR-103a-3p mimics, inhibitors, and PTEN overexpression. Additionally, a PCOS rat model was developed through TP injections, and rats were treated with metformin at varying doses. Cell viability, proliferation, and apoptosis were assessed using MTT, EdU, and TUNEL staining techniques. The results showed that TP treatment reduced KGN cell viability and promoted apoptosis, while metformin treatment restored cell viability and improved these markers. Altering miR-103a-3p levels or PTEN expression further modulated cell proliferation and apoptosis, supporting the involvement of the miR-103a-3p/PTEN axis in PCOS pathophysiology. In the rat model, metformin alleviated metabolic and reproductive dysfunctions by regulating key biomarkers. These findings suggest that metformin can promote granulosa cells proliferation and inhibit apoptosis, providing a promising therapeutic approach for PCOS through the miR-103a-3p/PTEN axis.