3). Difference from endometriosis and ovarian endometrioma
Why do different researchers study the relationship between endometriosis and autophagy, but come to the opposite conclusion? We speculate that in the occurrence and development of endometriosis, there are mechanisms of oxidative stress and anti-oxidation. Reactive oxygen species (ROS) are produced continuously in normal cell metabolism, which are considered as signal transduction functions. However, when excessive ROS is induced by environmental factors or diseases, oxidative stress will occur, which leads to autophagy, apoptosis, necrosis,,and other physiological and pathological processes.(73) the accumulated ROS activate TFEB through mTOR independent mechanism and induce autophagy to maintain energy metabolism and remove excessive ROS. Because ovarian endometriosis can form cysts easier and lead to blood accumulation, which can produce more ROS. Ruiz, A et al. found that the expression of lc3b protein in endometriosis mouse model was decreased (compared with the uterine horn isolated from the same disease treatment), while the lc3b level in the epithelial cells and eutopic endometrium of patients with endometriosis was higher than that in the control group. They speculate that this difference may be due to the fact that the lesions in mice are equivalent to those in patients with early endometriosis. Because human diseases can’t be diagnosed until a delay of 7-10 years.(48) This conjecture is similar to our hypothesis that autophagy is down-regulated in the early stage of endometriosis. As the disease progresses, the accumulation of ROS leads to the up regulation of autophagy, thus promoting the growth and infiltration of ectopic endometrial cells. Induction of autophagy may be beneficial to tumor prevention, Alternatively, it may promote tumor progression by enhancing autophagy-mediated intracellular circulation, which facilitates the removal of metabolic substrates and the preservation of mitochondrial functional pools.(8) There may be the same mechanism in occurrence and development of endometriosis that causes it to behave like a tumor.