Quercetin ameliorates PCOS ovarian fibrosis by modulating short-chain fatty acid synthesis via increased akkermansia muciniphila abundance
Abstract
Background: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder causing anovulatory infertility, characterized by critical ovarian fibrosis that impairs follicular development. Current pharmacological treatments for ovarian fibrosis in PCOS are limited. Quercetin, a natural flavonoid found in plants and traditional medicine, shows therapeutic promise for PCOS, though its direct effects on ovarian fibrosis and gut microbiota-mediated mechanisms remain unclear.
Methods: The PCOS mouse model was established by administering letrozole in combination with a high-fat diet. To determine the optimal therapeutic dosage, PCOS mice were randomly assigned to three quercetin treatment groups: low-dose group (PCOS + LT), medium-dose group (PCOS + T), and high-dose group (PCOS + HT). Body weight and serum hormone levels (LH, FSH, T and AMH) were systematically measured across all groups to determine the most effective concentration. Reproductive function was assessed by monitoring the estrous cycle (vaginal smears). Insulin resistance was evaluated using glucose tolerance test (GTT) and insulin tolerance test (ITT). After the medium dose was identified as the optimal intervention dose of quercetin, subsequent experiments were conducted to investigate the underlying mechanisms. Ovarian tissue was analyzed for morphology, inflammation and fibrosis. Additionally, the intestinal mucosal structure and permeability were examined. Feces were collected for comprehensive gut microbiota…
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