Macrophage Plasticity and Extracellular Vesicles in Endometriosis: Immunopathology and Therapeutic Perspectives

Endometriosis, as a chronic gynecological condition, includes irregular endometrial cell growth beyond the uterus, which creates pelvic pain and infertility, together with inflammatory disease throughout the body. Currently, about 10% of all women worldwide experience this disease, but scientists have not determined its natural causes. Importantly, the development of endometriosis depends significantly on the dysfunction of the immune system, which results in impaired macrophage activity. Specifically, endometriotic lesions contain M2-like macrophages, supporting tissue reconstruction along new blood vessel formation and evading immune responses. Moreover, the survival of lesions and the processes of neurogenesis and inflammation depend on the actions of macrophage-derived extracellular vesicles (EVs) as well as cytokines and growth factors. In this context, this review investigates the process of macrophage polarization and details the cellular interactions found in endometriotic tissue environments and their therapeutic capacity. Ultimately, understanding the underlying mechanisms of disease will facilitate the development of immunomodulatory therapies aimed at reducing symptoms and improving clinical outcomes.