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.