HYPOXIA AND REPRODUCTIVE HEALTH: The role of hypoxia in the development and progression of endometriosis

Endometriosis is a benign gynecological disease that affects about 10% of women of reproductive age. Patients with endometriosis suffer from long-term coexistence with dysmenorrhea, dyspareunia, and even infertility, which severely reduces quality of life. So far, surgical removal and hormonal medication are the major treatment options; however, high recurrence and severe adverse effects hamper the therapeutic efficacy. Hypoxia is an inevitable cellular stress in many diseases that regulates the expression of a significant subset of genes involved in pathophysiological processes. A growing body of evidence demonstrates that hypoxia plays critical role in controlling the disease phenotypes of endometriosis, such as increasing adhesion ability, causing dysregulation of estrogen biosynthesis, aberrant production of proinflammatory cytokines, increasing angiogenic ability, and suppression of immune functions. In this review, we summarize the findings of the most recent studies in exploring the underlying mechanisms of hypoxia involved in endometriosis. Potential therapeutic options for targeting HIF and downstream effectors will also be discussed.