MicroRNA Regulation of Ovarian Angiogenesis and Folliculogenesis in Bovine Cystic Ovarian Disease

Cystic ovarian disease (COD) is a major contributor of infertility in cattle, with both angiogenic and genetic contributions proposed. We hypothesized that miRNAs are integral to the regulation of ovarian function and that altered miRNA expression contributes to the onset and progression of reproductive disorders in cattle. miRNAs known to target VEGF or TSP-1 were analyzed in granulosa and endothelial cell lines treated with recombinant VEGF and 3TSR, which resulted in a significant increase in miR-15a, miR-29a, miR-126, and miR-132 expression. In addition, miRNA, mRNA, and protein expression levels were analyzed in large and cystic bovine follicles. VEGF and miR-29a were found to have enhanced expression, while miR-132 expression decreased in cystic follicles as compared to large. Our findings suggest that these miRNAs may play a role in maintaining the balance between VEGF and TSP-1 in the ovary, and if disrupted could potentiate ovarian-based reproductive disorders.