Progress in PCOS through investigation of the microbiome 3983

Abstract Description This study aims to explore the relationship between gut microbiome dysbiosis, inflammation, and the hypothalamic-pituitary-gonadal (HPG) axis in the context of Polycystic Ovary Syndrome (PCOS). We hypothesized that interference with the HPG axis due to gut microbiome dysbiosis and inflammation exacerbates metabolic and reproductive outcomes in PCOS. To test this, we used mice with Toll-like receptor 4 (TLR4) knocked out (TLR4-KO) and compared them to C57BL/6J wild type (WT) mice. PCOS was induced using letrozole pellets, with a placebo group for control. Over five weeks, we monitored weight, fasting blood glucose, and reproductive outcomes via vaginal lavages. Results indicated that TLR4-KO mice receiving letrozole gained less weight and had lower fasting blood glucose levels compared to WT mice. Additionally, TLR4-KO mice showed irregular, but present, estrus cycles, whereas placebo-treated WT mice were stuck in the resting stage. These findings suggest that knocking out TLR4 reduces inflammation, leading to improved PCOS-like symptoms. The study also aims to correlate changes in the gut microbiome with these improved outcomes, contributing to a better understanding of PCOS and potential new treatments. Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)