Research Advances in the Endometriotic Microenvironment: Synergistic Immune-Inflammatory-Angiogenic Interactions and their Therapeutic Translation.

Endometriosis (EM) is a chronic inflammatory disorder characterized by the ectopic growth of endometrial-like tissue outside the uterine cavity. Its pathogenesis is closely linked to an imbalanced immune–inflammatory–angiogenic microenvironment. Core pathological features include immune suppression (e.g., M2 macrophage polarization, regulatory T cell increase), chronic inflammation (e.g., elevated IL-6, TNF-α, NF-κB/NLRP3 activation), and hypoxia-driven aberrant angiogenesis via the VEGF/HIF-1α axis. These components interact through shared molecular pathways—such as HIF-1α and NF-κB synergistically upregulating VEGF—forming a self-sustaining feedback loop that promotes lesion growth, fibrosis, pain, and infertility. Recent studies have explored microenvironment-targeted therapies (e.g., immune checkpoint blockade, anti-angiogenics), though most remain preclinical. Challenges include optimizing treatment timing, overcoming resistance, and patient heterogeneity. Future research should leverage multi-omics and organoid models to decode EM microenvironment dynamics and advance precision medicine.