(P30-039-23) Omega-3 Fatty Acids Modulate Apoptosis and Angiogenesis Pathways in Endometriosis

Objectives: Endometriosis is a benign sex hormone-dependent gynecological disease characterized by the presence and growth of endometrial tissue outside the uterus and it is associated with infertility and pain. Despite the exact underlying mechanisms are unclear, confirmed evidences have shown that the inflammatory responses and pathological conditions such as neo-angiogenesis and fibrosis are main contributors. Omega 3 fatty acids limit inflammatory reactions, angiogenesis, cell proliferation and survival which may reduce progression of endometriosis. Understanding the exact mechanism underlying the effect of omega 3 fatty acids on endometriotic lesions can shed light the therapeutic strategies and move forward the science in this regard. Given together, we conducted present systematic literature review on relevant published studies to clarify the action points of omega 3 fatty acids on anti-apoptotic and anti-angiogenic signaling pathways in endometriosis.

Methods: All databases including PubMed, MEDLINE, EMBASE and Web of Science were searched until January 20^th, 2023.

Results: Omega 3 fatty acids suppress angiogenesis and inflammation through inhibiting production of angiogenic mediators including Vascular Endothelial Growth Factor (VEGF), Platelet-Derived Growth Factor (PDGF), Platelet-Derived Endothelial Cell Growth Factor (PDECGF), cyclo-oxygenase 2 (COX-2), 12/15-Lipoxygenase (12/15-LOX), prostaglandin-E2 (PGE2), nitric oxide, Nuclear Factor Kappa Beta (NFKB), matrix metalloproteinases (MMPs) and beta-catenin. Feeding with EPA and DHA as main omega 3 fatty acids derived from fish oil were found to induce ROS accumulation, oxidative stress, increase DNA fragmentation and caspase-8-dependent cell death. In addition, DHA decreases [methyl-(3)H]-thymidine uptake and expression of proliferation-associated proteins (proliferating cell nuclear antigen; PCNA, and proliferation-related kinase; PRK).

Conclusions: Based on experimental studies, omega 3 fatty acids can inhibit angiogenesis and cell proliferation in endometriotic lesions. Further clinical trials are needed to confirm these findings to adjuvant nutritional supplementation with omega 3 fatty acids to reduce the frequency of pain and improve the endometriotic tissue.

Funding Sources: This study is supported by Tehran University of Medical Sciences.