Autophagy is upregulated in ovarian endometriosis: a possible interplay with p53 and heme oxygenase-1

Objective: To evaluate the occurrence of the autophagic process in ovarian endometriomas compared with eutopic endometrium of affected women and with normal endometrium of healthy women. Design: Biochemical and molecular study in tissue extracts. Setting: University cellular pathology laboratory and university hospital. Patient(s): Patients with ovarian endometriosis (n = 13) and healthy women (n = 18). Intervention(s): Specimens of endometrium were obtained by hysteroscopy from patients with endometriosis and from healthy control subjects; specimens of ovarian endometriomas were collected by laparoscopy. All patients underwent surgery after the end of menstrual bleeding, resulting in most of our patients (approximately 80% in each group) being in the proliferative phase. Main Outcome Measure(s): Autophagy was evaluated by Western blot analysis of biochemical markers (LC3-II, LC3-II/LC3-I ratio and p62) and by quantitative real-time polymerase chain reaction of autophagy-related genes (ATG14, BECN1, ATG7, and LC3B); apoptosis-related (p53 and Bcl-2) and oxidative stress-related (heme oxygenase-1) proteins were also evaluated by Western blot analysis. Result(s): All tested biochemical markers and messenger RNA levels of autophagy-related genes showed a significant up-regulation of autophagy in ovarian endometriomas compared with eutopic endometria of affected or healthy women. Moreover, a significant decrease of p53 protein and a significant increase of heme oxygenase-1 protein was also evident in endometriomas. Conclusion(s): The upregulated autophagic process observed in ovarian endometriomas can be regarded as an integral part of endometriosis pathogenesis, possibly contributing to survival of endometriotic cells in ectopic sites and to lesion maintenance. The decreased susceptibility to apoptosis and the persistent oxidative stress experienced by endometriotic cells could favor autophagy stimulation. (C) 2015 by American Society for Reproductive Medicine.