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Ovarian Fragmentation and Hippo Signalling Disruption
The Hippo signalling pathway is an essential pathway involving several components that regulate cell growth, survival and stem cell renewal. For this reason, the Hippo signalling pathway has been implicated in the maintenance and control of organ size in organisms.

In recent years, ovarian fragmentation has surfaced as an effective strategy to promote ovarian follicular activation and growth. Studies undertaken on cultured human ovarian cortical fragments have demonstrated that the mechanical damage resulting from ovarian tissue fragmentation disrupts the Hippo signalling pathway. This has been found to accelerate follicle activation. Mechanical damage to the ovaries through fragmentation have been found to induce a transient elevation in actin polymerisation - a process where small actin molecules (proteins) combine to form a large, chain-like structure with repeating actin units. Mechanical damage to the ovaries has also decreased phosphorylation of Yes-associated protein (YAP), an essential compound in the Hippo Signalling pathway. Phosphorylation refers to the addition of phosphate groups to molecules. Consequently, this leads to an increase in the levels of YAP in the nucleus. This in turn triggers a downstream ripple effect to increase the expression of growth factors and apoptosis inhibitors, therefore promoting cell growth and survival.

PI3K/AKT/MTOR Signalling Pathway Activation
Another key pathway in ovarian follicle activation is the PI3K-PTEN-AKT-FOXO3 pathway.

The PI3K-PTEN-AKT-FOXO3 pathway is a complex signal transduction pathway involving a cascade of several molecules. This pathway is involved in promoting growth, survival and proliferation of cells in response to certain factors. The pathway is therefore implicated in the activation of ovarian primordial follicles. In in vitro activation of ovarian follicles, drugs such as inhibitors of PTEN or activators of PI3K can be administered to stimulate follicle activation.