Regulation of follicle growth through hormonal factors and mechanical cues mediated by Hippo signaling pathway.

The ovary is an interesting organ that shows major structural changes within a short period of time during each reproductive cycle. Follicle development is controlled by local paracrine and systemic endocrine factors. Many hormonal and molecular analyses have been conducted to find the mechanisms underlying structural changes in ovaries, However, exact mechanisms still remain to be determined. Recent development of mechanobiology facilitates the understanding on the contribution of physical forces and changes in the mechanical properties of cells and tissues to physiology and pathophysiology. The Hippo signaling pathway is one of the key players in mechanotransduction, providing an understanding of the molecular mechanisms by which cells sense and respond to mechanical signals to regulate cell proliferation and apoptosis for maintaining optimal organ sizes. Our group recently demonstrated the involvement of the Hippo signaling pathway in the regulation of ovarian follicle development. Fragmentation of ovarian cortex into small cubes changed cytoskeletal actin dynamics and induced disruption of the Hippo signaling pathway, leading to the production of CCN growth factors and anti-apoptotic BIRC. These factors, in turn, stimulated secondary follicle growth in vitro and in vivo. In this review, we summarized hormonal regulation of follicular structural changes and further focused on the role of Hippo signaling in the regulation of follicle development. We also suggest a new strategy of infertility treatments in patients with polycystic ovary syndrome and primary ovarian insufficiency based on mechanobiology.