Autophagy in ovary: protective roles, pathological consequences, and unresolved issues

The ovaries play essential roles in providing oocytes for fertilization and secreting sex hormones that regulate various organ functions. Autophagy has been implicated in the modulation of ovarian functions, yet its mechanisms of action are complex and context-dependent. Within the ovary, autophagy fulfills a dual function, serving as a critical mechanism in facilitating oocyte development, maintaining granulosa cell viability, regulating hormone synthesis, ovulation and luteal function. Conversely, dysregulation of autophagy can interact with other death signals, leading to cell death of ovarian cells, and has been linked to the development of diminished ovarian reserve (DOR), premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS). Emerging evidence suggests that pharmacological modulation of autophagy exerts significant therapeutic effects on POI and PCOS. Despite this association, numerous unresolved issues persist in this field of research. This paper provides a comprehensive overview of the context-dependent roles of autophagy in ovarian physiology and disorders, and proposes potential applications of autophagy-based interventions as therapeutic strategies for addressing ovarian dysfunctions.