Exosomal MicroRNA-424-5p From Polycystic Ovary Syndrome Follicular Fluid Attenuates Ovarian Inflammation via Targeting the Fibroblast Growth Factor 2/Fibroblast Growth Factor Receptor 1 Axis

Abstract

Sustained low-grade inflammation is increasingly recognized as a central element in how polycystic ovary syndrome (PCOS) develops. Here we set out to clarify what role follicular fluid (FF)-borne exosomal miR-424-5p plays in shaping ovarian inflammation and how this ties in with the ovulatory problems seen in PCOS. Across FF samples taken from patients, miR-424-5p levels tracked inversely with pro-inflammatory cytokine concentrations to a striking degree. When granulosa cells (GCs) were challenged with lipopolysaccharide (LPS), delivering exosomal miR-424-5p dampened cytokine release and restored the expression of ovulation-linked genes. Using a dual-luciferase reporter assay, we traced this effect to FGF2, which miR-424-5p binds directly, and we found FGF2/FGFR1 signaling to be conspicuously raised in PCOS. In dehydroepiandrosterone (DHEA)-treated rats modeling the syndrome, giving exosomal miR-424-5p eased ovarian inflammation and brought back part of the lost ovulatory capacity. Taken together, the data suggest that exosomal miR-424-5p tempers ovarian inflammation in PCOS by holding the FGF2/FGFR1 axis in check, which casts fresh light on the follicular abnormalities that mark this condition.