The Role Of Endoplasmic Reticulum Stress And PI3K/Akt Pathway In The Occurrence Of Endometriosis

Background:Endometriosis (EMs) is a common gynecologic disorder of reproductive-aged women, causing symptoms such as infertility, dysmenorrhea and chronic pelvic, which severely impacts the quality of life. Although EMs is one of the most investigated disorders of gynecology, its pathogenesis still remains elusive. In pathological morphology, it is regarded as a benign disease; however, it shares similar characteristics with malignant tumors:planting, invasive and distant metastasis. Nowadays much more attention than ever before has been taken upon the relationship between EMs and apoptosis. A great deal of research enunciations that there is an intimate relationship between cell apoptosis and the occurrence and development of EMs. Endoplasmie reticulum stress (ERS) is a newly reported cell apoptosis pathway, which triggers an conserved mechanism called the unfolded protein response(UPR). ERS is closely related to the occurrence and development of tumor as well as cell apoptosis. GRP78, as the main molecular chaperone of the inducible expression of ERS, has a protective effect to tumor cells, and it is indicated that its overexpression is in correlation with the inhibition of apoptosis. PI3K/Akt pathway is the key signal pathway to regulate the proliferation, differentiation, apoptosis and senescence of cells. AKT, a critical anti-apoptotic signal molecules, shows abnormal regulation in various tumor tissues, such as ovarian cancer, breast cancer, endometrial cancer, etc. And studies have reported that PI3K/Akt pathway has important significance to the occurrence and development of EMs. An enhancement of the activity of PI3K/Akt can be observed in EMs. ERS has already been widely applied in the field of tumor. It has already been reported that ERS is activated in various tumor cells. UPR promotes the grouth of tumor with the occurrence and development of tumor. But its effects on EMs remain uncovered. This study is to explore the roles of ERS and PI3K/Akt pathway in the occurrence and development of EMs by detecting the expression of clinical specimens of GRP78and AKT.Objectives:Investigate the expression and localization of GPR78and AKT respectively in women with and without EMs, and explore their relationship with the occurrence and development of EMs initially.Methods:Samples were collected between June2009and June2011at the Women’s Hospital, Zhejiang University Medical College. Ectopic and homologous eutopic endometriums from42women with EMs were taken as the study group(including26cases in proliferative phase,16in secretory phase;12cases in clinical stage Ⅰ～Ⅱ,and30in clinical stage Ⅲ～Ⅳ), with another38endometriums from women without EMs as the control(including24cases in proliferative phase,14in secretory phase). The expression of GRP78and AKT of the two groups has been under detection by immunohistochemical method (Envision2-step method). All statistical analysis was performed via SPSS16.0. Differences were considered to be significant when P<0.05.Results:1、GRP78and AKT were mainly located in cytoplasm and cytomembrane of glandular epithelium cells in the eutopic、ectopic and normal control group. There Was only a little expression in stromal cells.2、The expression of GRP78in eutopic endometriums and the ectopic ones was higher than that of the normal control group (P<0.01), but there were no significant differences between ectopic endometrium and eutopic endometrium of EMs (P>0.05). Furthermore, a cyclic variation during the menstrual cycle phases of the normal control group is observed and the expression of the epithelial cells was higher in the secretory phase than in the proliferative phase. But we did not find the same phenomenon in the ectopic and eutopic endometrium of EMs.3、The expression of AKT in eutopic endometriums and the ectopic ones was higher than that of the normal control group (P<0.01). But there were no significant differences between ectopic endometrium and eutopic endometrium of EMs (P>0.05). Also, no relationship between the expression of AKT and the menstrual cycle was found.4、No statistically significant differences were found in the eutopic and ectopic endometrial expression of GRP78and AKT between Ⅰ～Ⅱ stage and Ⅲ～Ⅳstage of EMs (P>0.05).5、Positive correlation was found between the expression of GRP78and AKT in the ectopic endometrium of EMs (P<0.01). On the contrary, no correlation between the two was proved in the eutopic endometrium of EMs (P>0.05).Conclusions:1、In EMs, the increasing expression of GRP78and AKT in eutopic and ectopic endometriums results in the strength of endometrial tissue against apoptosis. Maybe there has a mutual effect of the ERS and the PI3K/Akt signal path in the pathogenesis of EMs.2、The expression of GRP78and AKT maybe has no significant relationship in the development of EMs.