Non-hormonal pathogenic pathway in endometriosis tissue

The term "non-hormonal pathogenic pathway in endometriosis tissue" refers to all molecular and cellular mechanisms contributing to the establishment, survival, and progression of endometriotic lesions that do not directly involve classical estrogen/progesterone signaling. These include: - Inflammatory cascades and immune cell recruitment, with cytokines and chemokines driving chronic inflammation and altering local tissue environments (e.g., TNF-α, IL-6, TGF-β)[5][6]. - Extracellular matrix (ECM) remodeling, driven by matrix metalloproteinases (MMPs) and their regulators, facilitating lesion invasion and fibrosis[1][5]. - Epigenetic modifications (e.g., altered DNA methylation, histone modification, and microRNA expression), which can modulate gene expression patterns and thus the cellular phenotype of endometriotic tissue[3][4][5]. - Oxidative stress, often related to iron overload in lesions, which can contribute to cellular injury, impaired differentiation, and pain[5]. - Angiogenesis and neurogenesis, mainly via non-steroidal local growth factors (like VEGF) and neuronal factors, promoting lesion vascularization and nerve infiltration, furthering pain and lesion maintenance[5][6]. Current research focuses on identifying specific molecular targets within these non-hormonal pathways for new drug development, aiming to overcome the limitations of hormone-based therapies and provide options for women who wish to preserve fertility or experience contraindications to hormonal drugs[6]. However, the umbrella term does not refer to a singular, canonical target, thus it is not a valid input for structured molecular target databases.