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.