MicroRNA Profiles of Human Follicular Fluid Extracellular Vesicles Reveal Stress Response Pathways and Role in Ovarian Aging

This microenvironment consists of extracellular vesicles in the follicular fluid. Follicular fluid extracellular vesicles (FF-EVs) are important communication mediators between ovarian somatic cells and the oocyte that could be playing a role in the changes of the follicle microenvironment as the ovary ages.

To elucidate mechanisms that contribute to the age-related decline of oocyte quality, we characterized EVs and sequenced the small-RNA cargo from young (<32 y.o.) and AMA (>38 y.o.) patients' follicular fluid. We identified 23 differentially expressed microRNAs (DE miRNAs), specifically 12 downregulated and 11 upregulated, in young compared to aged FF-EVs (P value < 0.05, FDR < 0.10, Fold Change > 2). Target gene prediction and pathway analysis indicate up- and downregulated miRNAs target genes associated with oxidative stress response, such as the AGE-RAGE and HIF-1 signaling pathways.