Oral Contraceptive Use Is Associated with Significant Differences in MicroRNA Cargo of L1CAM-Associated Extracellular Vesicles

Oral contraceptives (OCs) are approved for use after onset of menarche, which is well before brain maturation is complete. OC use may induce biochemical changes in the brain, especially during the neurobiologically dynamic adolescent/young adult years. MicroRNA cargo in L1CAM-associated extracellular vesicles was measured from serum samples collected from young women using the miRCURY LNA miRNA Focus PCR Panel (Qiagen) and validated using quantitative PCR. Linear regression and F-tests were applied to identify differentially expressed microRNAs by OC use (never versus current), and PANTHER pathway analysis was conducted on the gene targets of significantly differentially expressed microRNAs. Twelve microRNAs had significant differential expression variability by OC use (Bonferroni adjusted p < 0.002). Pathway analysis revealed that the 1254 unique genes targeted by the significant microRNAs were most enriched for the Gonadotropin-releasing hormone receptor pathway (FDR q = 5 x 10-7), which is associated with the release of gonadotropins, pubertal development, and reproduction. The results are consistent with the hypothesis that microRNA cargo in circulating extracellular vesicles may reflect brain-related biological activity and that OC use may influence extracellular vesicle cargo composition. The significant difference in expression variability may have implications for designing future studies, including power calculations.