FIGURE 3.

Cell death pathways utilized by oocytes and granulosa cells. The intrinsic apoptotic pathway is elicited through growth factor deprivation or cytotoxic stimuli. Signals are transduced via the phosphoinositide-3-kinase (PI3K) pathway converging on the transcription factor forkhead box O3 (FOXO3) whose targets include BCL2 family proteins and death receptor ligands, causing an imbalance in BCL2 family proteins, activating effector caspases, and leading to apoptosis. Effector caspases are also activated via the extrinsic apoptotic pathway when death receptor ligands binding their corresponding receptors on the cell membrane. Death receptor signaling can also result in BH3 interacting-domain death agonist (BID) cleavage by caspase-8, leading to the generation of active tBID, and cross talk with the intrinsic apoptosis pathway. Finally, BCL2 can interact with Beclin 1 to regulate autophagy, and downstream ATG proteins and LC3-II act to control autophagosome formation. Image created with BioRender.com, with permission.