Ovulation: A consequence of acute inflammation cultivated by E2-induced reactive oxygen species and triggered by progesterone withdrawal.

Ovulation is a complex biological process essential for female fertility, driven by the luteinizing hormone (LH) surge and involving a cascade of molecular events that lead to follicular rupture and oocyte release. This process shares characteristics with acute inflammation, including the generation of reactive oxygen species (ROS) by E2, immune cell recruitment, and tissue remodeling. E2 enhances mitochondrial ROS production through integrin-dependent signaling, regulating key ovulatory events such as cumulus expansion and extracellular matrix breakdown. The LH surge triggers follicular luteinization and progesterone production, which are critical for preparing the endometrium for implantation and modulating inflammation. Progesterone, acting through its receptor (PGR), suppresses ROS-induced inflammation by inhibiting the NF-κB pathway, ensuring controlled inflammatory responses. However, a transient decline in progesterone levels following the LH surge initiates acute inflammation, leading to follicle rupture and ovulation. This process involves the upregulation of matrix metalloproteinases and other proteases that degrade the follicular wall, facilitated by structural changes such as cumulus expansion and decellularization at the follicular apex. Post-ovulation, the remaining follicular cells undergo luteinization to form the corpus luteum, which produces progesterone to support early pregnancy. The ovulation wound heals rapidly through a process resembling ordinary wound healing where follicular fluid plays a dual role by promoting ovulation wound healing and when spilled into the pelvic cavity, potentially contributing to postoperative adhesions. Understanding the molecular mechanisms of ovulation provides valuable insights into fertility promotion, contraception development, and the prevention of reproductive disorders.