Rachel Stading

Introduction. Endometriosis is a chronic disease in which uterine tissue is implanted outside of the uterus¹. This disease affects one in every 10 women². The risk of endometriosis increases with increasing ovulatory cycles; therefore, women with less pregnancies or irregular menstrual cycles may be at higher risk of developing the disease³. Endometriosis often presents as asymptomatic; however chronic pelvic pain, dysmenorrhea, dyspareunia, dyschezia, and subfertility are common symptoms that may indicate endometrial tissue development³. For diagnosis of endometriosis, surgical biopsy and pathological analysis are required^2,4. However, pain levels as well as pelvic and transvaginal ultrasonography may give the physician some indication of the diagnosis^2,4. Methods. Generation of reactive oxygen species (ROS) in endometrial tissue contributes to the inflammation experienced in endometriosis by forming DNA adducts as well as disulfide bonds between thiols^1,5. Excess ROS produces oxidative stress and may be caused by an imbalance between oxidation and reduction enzymes¹. Studies examined this shift between oxidative and antioxidant enzymes as well as the alteration of ROS production in mitochondria in endometrial tissue^1,6. Other studies examined the relationship between oxidative stress produced in endometrial tissue and its contribution to infertility and tumorigenesis^7,8. Results. Based on the results of the study, phase I (oxidative) CYP450 enzymes, specifically CYP1A1 and CYP3A7, showed an increase in endometrial tissue compared to normal tissue¹. Furthermore, phase II (antioxidative) enzymes showed a decrease in endometrial tissue¹. Mitochondria was also found to contribute to ROS production through mitochondrial elongation⁶. Oxidative stress produced by endometrial tissue demonstrated a decrease in tumor suppressor genes as well as antioxidant enzymes⁷. Finally, ROS exposure in endometrial granulosa cells induced senescence, inhibiting viability of these cells⁸. Conclusion. These results indicate the importance of antioxidant and oxidant enzyme levels in the contribution to excess ROS and resulting oxidative stress in endometriosis. This oxidative stress may have many adverse consequences, such as inflammation as well as contributions to tumorigenesis and infertility. Enzyme level regulation may offer one possible mechanism in which inflammation caused by endometriosis could be controlled. This potential treatment method offers hope in reducing pain associated with this chronic disease and warrants further exploration.

1. Hevir N, Ribic-Pucelj M, Rizner TL. Disturbed balance between phase I and II metabolizing enzymes in ovarian endometriosis: A source of excessive hydroxy-estrogens and ROS? Molecular and Cellular Endocrinology. 2013; 367:74-84. doi: 10.1016/j.mce.2012.12.019.
2. Bulun SE, Yilmaz BD, Sison C, Miyazaki K, Bernardi L, Liu S, Kohlmeier A, Yin P, Milad M, Wei JJ. Endometriosis. Endocr Rev. 2019; 40(4):1048-1079. doi: 10.1210/er.2018-00242.
3. Falcone T, Flyckt R. Clinical Management of Endometriosis. Obstet Gynecol. 2018; 131(3):557-571. doi: 10.1097/AOG.0000000000002469.
4. Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med. 2020; 382(13):1244-1256. doi: 10.1056/NEJMra1810764.
5. Turkyilmaz E, Yildirim M, Cendek BD, et al. Evaluation of oxidative stress markers and intra-extracellular antioxidant activities in patients with endometriosis. Eur J Obstet Gynecol Reprod Biol. 2016;199:164-168. https://www.sciencedirect.com/science/article/abs/pii/S030121151630063X. Accessed April 13, 2021.
6. Chen C, Zhou Y, Hu C, et al. Mitochondria and oxidative stress in ovarian endometriosis. Free Radic Biol Med. 2019;136:22-34. https://doi.org/10.1016/j.freeradbiomed.2019.03.027. Accessed April 13, 2021.
7. Winarto H, Tan MI, Sadikin M, et al. ARID1A Expression is Down-Regulated by Oxidative Stress in Endometriosis and Endometriosis-Associated Ovarian Cancer. Transl Oncogenomics. 2017;9:1177272716689818. https://pubmed.ncbi.nlm.nih.gov/28469404/. Accessed April 13, 2021.
8. Lin X, Dai Y, Tong X, et al. Excessive oxidative stress in cumulus granulosa cells induced cell senescence contributes to endometriosis-associated infertility. Redox Biol. 2020;30:101431. https://pubmed.ncbi.nlm.nih.gov/31972508/. Accessed April 13, 2021.