Modulation of PI3K/AKT/mTOR signaling pathway by combined stem cell and phytochemical treatment improves metabolic and reproductive outcomes in PCOS

作者：Jixiang Chen, Lihua Zhang, Jing-li Gan, Xueyan Teng, Xiaohong Huang, Jiaqing Lv, Hao Li · 发表于：Journal of Ovarian Research · 年份：2025 · DOI：10.1186/s13048-025-01910-0 · 被引用次数：3 · 研究领域：Reproductive Biology and Fertility、Ovarian function and disorders、Ovarian cancer diagnosis and treatment

BACKGROUND: PCOS is characterized by ovulatory dysfunction and metabolic abnormalities, and growing evidence suggests that dysregulated autophagy in ovarian granulosa cells contributes to its pathogenesis. Mesenchymal stem cells (MSCs) and Medicine Lin (ML) therapy have been proven to improve these dysfunctions in PCOS patients, enhancing fertility and pregnancy outcomes, though their underlying mechanisms remain unclear. This study hypothesized that MSCs and ML function by regulating the autophagy-mediated PI3K/AKT/mTOR signaling pathway. METHODS: A PCOS mouse model was established through high-fat, high-sugar diet and letrozole induction. MSCs and ML treatment was administered for three weeks, followed by fertility testing. Ovarian morphological changes were examined using H&E and Masson staining, autophagosomes in granulosa cells were observed via transmission electron microscopy, serum hormone levels were measured by using ELISA kits, fetal umbilical blood flow was monitored with Doppler ultrasound, cell apoptosis and LC3II expression in ovarian and placental tissues were evaluated using TUNEL and immunofluorescence, and Western blot was used to analyze expressions of PI3K, AKT, FOXO1, mTOR, S6K1, Beclin1, P62, LC3II / LC3I, and ROS. RESULTS: Combined MSCs and ML therapy significantly improved glucose and lipid metabolism, reduced androgen levels, and addressed key endocrine disruptions. This combined therapy reduced ovarian collagen fiber formation and excessive autophag...