Figure 4. Possible signaling pathways that mediate FSH-induced meiotic resumption in COCs in vitro.

FSH acts through the downstream mediators PKC δ and θ, which recruit the cytosolic components p47^phox and p67^phox to the plasma membrane, allowing their combination with membrane components of NOX to form an active enzyme system to generate ROS. Then, ROS activate TACE by oxidizing the inhibitory prodomain to expose the catalytic domain. Next, the activated TACE via ROS cleaves pro-EGF-like factors into soluble EGFR ligands, which bind to and activate EGFR in an autocrine mode, thereby resulting in oocyte maturation.