**4. The possible role of clinically relevant different gene in endometriosis pathogenesis**

The difference in the screened genes, tissue inhibitor of metalloproteinase 3 (TIMP-3) both in the Han chinese and Uyghur with endometriosis were down-regulated. The study of Zhou Honghui found that TIMP-3 down-regulation is remarkable in the secretory phase than proliferative phase. TIMP is a metalloproteinase (MMPs) inhibitors by the endometrial cells of MMPs which plays an important role in the invasion of the peritoneum and other connective tissue. Increased endometrial MMPs and TIMP down-regulation with the development of endometriosis is closely related. Because of TIMP up-regulation and MMPs down-reglation, ectopic endometrial of endometriosis is more invasive than normal force, and develop to the peritoneal endometriotic lesions.Angiogenesis is considered as a major process in the pathogenesis of endometriosis. Many factors are involved in this complex mechanism, and the vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis; it is a potent endothelial cell mitogen, morphogen, and vascular permeabilityinducing agent. VEGF binds to either of two tyrosine kinase receptors, the fm5-like tyrosine kinase (flt) and the kinase domain receptor (KDR or Flk-1). Peritoneal endometriotic lesions with high proliferative activity are also accompanied by high angiogenic activity, as reflected by higher expression of VEGF-A in stroma and glandular epithelium and VEGFR-2 in blood vessels. In our recent study, we showed that the vascular density and the expression of VEGF and its receptor VEGFR-2 (Flk-1) are significantly higher in deeply infiltrating endometriosis affecting the ovary, bladder and mainly the rectosigmoid, compared with the ectopic endometrium.

Controlled clinical analyses of angiogenesis in human endometriotic lesions are limited, because it is not possible to monitor the lesions without repeated laparoscopies. Thus, research into the fundamental mechanisms by which menstrual endometrium adheres, invades and establishes a functional vasculature to persist in an ectopic site, as well as the development of new therapeutical approaches, is best performed in experimental animal models. In contrast to humans and non-human primates, estrous animals do not shed their endometrial tissue and therefore do not develop endometriosis spontaneously. However,

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endometriosis can be induced by transplanting endometrial tissue to ectopic sites, and the establishment of an experimental model of endometriosis may be a good way to study the endometriosis angiogenesis process, and allow evaluation of the balance of the many factors involved.

This study by glyceraldehyde 3-phosphate dehydrogenase (GAPD) gene in Han chinese and Uyghurs with endometriosis group are down-regulated, GAPD genes are housekeeping gene family, Gene bank No. NM-002046, is a basic enzyme in the human body.It is a key enzyme of a series of biochemical reactions of the glycolysis, which generate ATP for the source of human cells energy, a variety of cells are present in the body, involved in glucose metabolism in glycolysis, in 12p13.

In Han and Uyghur groups the same set of common up-regulated genes are GNGS, VIM and PRS23. Abundance or localization changes in endometrial tissue were validated by immunohistochemistry and Western blotting. In addition, multiple charge and size isoforms were observed for VIM in endometriosis patients that was below the level of detection in healthy women.

Our experiment confirmed endometriosis may be related to multiple factors similar as diabetes, asthma, cancer-related disease, genetics and aberrant regulation in the endometrium and endometriotic. Lower different genes expression on Uyghur women with endometriosis compared to Han Chinese women with endometriosis may be the essential factor for relatively lower incidence of endometriosis on Uyghur women. Most genes we found on the endometrium of both Uyghur and Han Chinese women with endometriosis were the cytoskeleton, adhesion, invaded and immune related gene,patially explained the mechanism of malignant biological behaviors.
