Ovarian fibrosis: Mechanistic insights and emerging therapeutic horizons

Ovarian fibrosis is one of the common pathological manifestations of many gynecological diseases, such as premature ovarian failure (POF), ovarian endometrioid cyst (OE), polycystic ovary syndrome (PCOS), radiotherapy and chemotherapy complications, which can cause ovarian fibrosis. Specifically, ovarian damage exceeds the repair capacity of surrounding parenchymal cells. In order to maintain the integrity of the tissue structure, a large amount of extracellular matrix is produced and over-deposited, which eventually leads to irreversible repair of the ovary and ovarian fibrosis. The prevalence and complexity of ovarian fibrosis, as well as its significant impact on female reproductive health, make it particularly important to further study its influencing factors and develop effective treatment strategies. We reviewed the intricate mechanisms driving ovarian fibrosis, including epigenetic modifications, transcriptional alterations, inflammatory responses, oxidative stress, iron overload, and extracellular matrix remodeling. These factors synergistically advance the disease's progression. This paper elucidates the aforementioned mechanisms to guide targeted therapy development. It also evaluates current diagnostic and therapeutic approaches and presents a list of novel targets for more effective treatment strategiesWe underscored the multifaceted nature of ovarian fibrosis and the imperative for tailored therapeutic approaches. By integrating molecular mechanisms with clinical insights, this review intends to set the stage for precision medicine, enhancing fertility and quality of life for women afflicted by ovarian fibrosis.