Clinical Relevance of Modifying RANKL Signaling During Folliculogenesis

Female infertility presents a significant societal challenge that will be aggravated in the future due to delayed parenthood. Our translational research suggests that receptor activator of NF-κB ligand (RANKL) is a novel treatment target, during assisted reproductive techniques and that inhibition of this pathway may reduce the impact of aging on the ovary. RANKL is a regulator of bone health, and an antibody (denosumab) blocking RANKL activity is used clinically to treat osteoporosis. Previously, we have shown that inhibition of RANKL increases sperm production in rodents, in human tissue models, and in a subpopulation of infertile men. Now, we show that all factors of the RANKL signalling system are expressed in human and mouse ovaries. Granulosa cell-specific Rankl knockdown lowers the number of primordial follicles, which suggests that RANKL has an important role during early stages