Correlation Of Angiogenic Factors In Pathological Process Of Endometriosis

Endometriosis(EMS) is a genetic, immunological, organs and hormone-dependent common gynecological disease with an incidence rate of 10% ~15% in the general population. EMS is characteristized by benign morphologic pathology but with a similar cancer-prone feature of easy planting, invasion and distant metastasis and high relapse rate.The pathological mechanisms of EMS remain unclear, leading to the lack of effective assessment and treatment of susceptible populations in clinical practice. The planting theory considers that the endometrium within the blood results countercurrent planting through the fallopian tubes, in addition, which is also supported by the iatrogenic cultivation theory. Recent studies show that estrogen receptors play a key role in the pathogenesis of endometriosis process. Ectopic endometrial tissues express high levels of estrogen receptors and grow in an estrogen-dependent manner. A growing number of researchers believe that the establishment of a new blood supply is essential for ectopic implantation endometrium, the development of endometriosis, therefore, is one of the key mechanisms of angiogenesis. A variety of angiogenic-related factors, including HIF-1α,VEGF and PDGF has been found dysregulated in EMS.Taken together, in the process of EMS, the correlation of the ischemia and hypoxia of the endometrium fragment, HIF-1α, ER, and the angiogenic factors is unclear. Hence, in this study, we discussed the correlation of Estrogen/ER, HIF-1α,VEGFand PDGF, to explore the novel mechanism of endometrisis.Aims:We aim to explore the correlation between ER, estrogen levels, HIF-1α, VEGF,PDGF, and verify the possible mechanism through HIF-1α, VEGF, PDGF axis to promote angiogenesis in endometriosis by in vitro experiments.Methods:Endometriosis tissues including ectopic endometrial cysts and in situ endometrium were collected, using uterine fibroids in patients with cervical intraepithelial neoplasia as a control. Estrogen levels were detected by CLIA method, and quantitative PCR were used to detect HIF-1α, VEGF, PDGF, and ERα and ERβ expression, and statistical analysis of the differential expression and correlation were also performed.Results:1) The level of expression of estrogen E2 in patients with uterine fibroids and endometriosis was higher than that in CIN. E2 levels were not significantly different between patients with endometriosis and fibroids.2) q RT-PCR results showed that VEGF and HIF-1α were highly expressed in the endometrium of endometriosis compared with endometrial uterine fibroids, and there was no significant difference in the level of PDGF.3) ERβ level was elevated in the endometrium of endometriosis, while ERα had no significant change, ERβ/ERα rate also largely increased in endometriosis; and ERβ had a higher expression in ectopic endometrium than that in in situ endometrium of endometriosis.4) Correlation analysis showed that HIF-1α was positively correlated with ERβ, and VEGF was positively correlated with ERβ in endometriosis.Conclusions:In summary, we speculated that in the pathological processes of endometriosis,endometrial debris that reverse influx into the abdominal cavity underwent the ischemia and hypoxia, which induced the pathological increasement of HIF-1α and ER and the positive feedback between them. And then the pro-angiogenic factors such as VEGF,PDGF in these debris were enhanced to promote endometrial ectopic attachment,microvascular formation and also its ectopic survival. Of course, the further experiments were needed to confirm this speculation.