**1. Introduction**

354 Endometriosis - Basic Concepts and Current Research Trends

Suzuki, T., Izumi, S., Matsubayashi, H., Awaji, H., Yoshikata, K., Makino, T. (2005). Impact

Torres, M.J.G., Acien, P., Campos, A., Velasco, I. (2002). Embryotoxicity of follicular fluid in

Toya, M., Saito, H., Ohta, N., Saito, T., Kaneko, T., & Hiroi, M. (2000). Moderate and severe

Zhang, X., Yao, H., Huang, X., Lu, B., Hong Xu, H., & Zhou, C. (2010). Nerve fibres in

fertilization*. Fertil. Steril.,* Vol. 83, pp. 908-13, ISSN 1556-5653.

pp. 344 –50, ISSN 1556-5653.

Vol. 25, pp. 392–397, ISSN 1460-2350.

populations. Hum. Reprod., Vol. 17, pp. 777-781, ISSN 1460-2350.

of ovarian endometrioma on oocytes and pregnancy outcome in in vitro

women with endometriosis. Its relation with cytokines and lymphocytes

endometriosis is associated with alterations in the cell cycle of granulosa cells in patients undergoing in vitro fertilization and embryo transfer. *Fertil. Steril.,* Vol. 73,

ovarian endometriotic lesions in women with ovarian endometriosis. *Hum. Reprod.,*

Endometriosis (EM) is a common and important health problem, it is estimated to be present in 10%-15% of women in the reproductive age group and 25%-35% of infertile women. In the First Affiliated Hospital of Xinjiang Medical University in China, 447 cases primaily diagnosed with surgically confirmed endometriosis between January 2000 to September 2005, among them 349 cases of endometriosis were Han Chinese (78.1%) and 69 cases Uyghur women with endometriosis (15.3%).

Fig. 1.

Xinjiang is the biggest province of China inhabited by ethnic minorities in which Uyghur people are accounted for more than 40% of the total population. In recent years, the number of the Uyghur women with endometriosis have been increased in Xinjiang, however still clearly less than Han chinese with endometriosis. The data from pathology deparment of the First Affiliated Hospital of Xinjiang Medical University between 1992 and 1996 showed that there were only three Uyghur women with endometriosis (5.76%) among 52 cases. Between 2000 and 2001, only 4 Uyghur women with endometriosis (3.1%) among 128 patients. Between 2003 and 2010, there were 73 Uyghur women (13.45%) with endometriosis

Analysis of Differential Genes of Uyghur Women with Endometriosis in Xinjiang 357

维 维 维

Fig. 4. Han with and without endometriosis ectopic endometriosis hybrid.

Fig. 5. Uyghur with and without endometriosis ectopic endometriosis hybrid before and

after correction signal strength distribution.

in 565 cases. In Kashi, the Uyghur is occupied more than 80% of population. In the last 8 years, there were only 16 Uyghur women with endometriosis among 600 cases of endometriosis in People's Hospital of Kashi. It was demonstrated that the number of Uyghur women with endometriosis dramaticaly lower than Han chinese.

We performed At1asTMcDNA Expression Arrays (Clontech # 7854-1) cDNA microarray (containing 22,000. DNA)to compare the differential expression genes between ectopic endometrium of Uyghur and Han chinese women with endometriosis. Our study aimed to explore the molecular pathogenesis of endometriosis ethnic differences, so as to determine the cause of endometriosis of Uyghur women in Xinjiang.

Fig. 2. Total RNA results.

Fig. 3. Uyghur with and without endometriosis ectopic endometriosis hybrid.

in 565 cases. In Kashi, the Uyghur is occupied more than 80% of population. In the last 8 years, there were only 16 Uyghur women with endometriosis among 600 cases of endometriosis in People's Hospital of Kashi. It was demonstrated that the number of

We performed At1asTMcDNA Expression Arrays (Clontech # 7854-1) cDNA microarray (containing 22,000. DNA)to compare the differential expression genes between ectopic endometrium of Uyghur and Han chinese women with endometriosis. Our study aimed to explore the molecular pathogenesis of endometriosis ethnic differences, so as to determine

> 维 维 维

Uyghur women with endometriosis dramaticaly lower than Han chinese.

Fig. 3. Uyghur with and without endometriosis ectopic endometriosis hybrid.

the cause of endometriosis of Uyghur women in Xinjiang.

Fig. 2. Total RNA results.

Fig. 4. Han with and without endometriosis ectopic endometriosis hybrid.

Fig. 5. Uyghur with and without endometriosis ectopic endometriosis hybrid before and after correction signal strength distribution.

Analysis of Differential Genes of Uyghur Women with Endometriosis in Xinjiang 359

Fig. 8. Han with and without endometriosis ectopic endometriosis hybrid before and after

**ID Name Cy5/Cy Description** 

1900 GNG5 1.211619 Guanine nucleotide binding protein (G

13167 IGFBP7 1.114798 Insulin-like growth factor binding protein 7

type IV,

8626 GAPD -2.01536 Glyceraldehyde-3-phosphate dehydrogenase 22689 GAPD -2.30404 Glyceraldehyde-3-phosphate dehydrogenase 22785 GAPD -2.71698 Glyceraldehyde-3-phosphate dehydrogenase

Table 1. Uyghur with and without endometriosis ectopic endometriosis differential genes.

22665 TIMP3 -1.15294 Tissue inhibitor of metalloproteinase 3

1527 XCL1 1.169442 Small inducible cytokine subfamily

1651 RPS23 1.093641 Ribosomal protein S23

21389 RPL29 -1.63396 Ribosomal protein L29

4340 FOS 3.649786 V-fos FBJ murine osteosarcoma viral oncogene homolog

protein),gamma 5

13265 COL3A1 -1.55893 Collagen,type III,alpha 1 (Ehlers-Danlos syndrome

autosomal dominant)

C,mendometriosisber 1 (lymphotactin)

correction signal scatter.

7224 DCN 2.250099 Decorin 10599 VIM 1.629836 Vimentin

Fig. 6. Han with and without endometriosis ectopic endometriosis hybrid before and after correction signal strength distribution.

Fig. 7. Uyghur with and without endometriosis ectopic endometriosis hybrid before and after correction signal scatter.

 Fig. 6. Han with and without endometriosis ectopic endometriosis hybrid before and after

Fig. 7. Uyghur with and without endometriosis ectopic endometriosis hybrid before and

correction signal strength distribution.

after correction signal scatter.

Fig. 8. Han with and without endometriosis ectopic endometriosis hybrid before and after correction signal scatter.


Table 1. Uyghur with and without endometriosis ectopic endometriosis differential genes.

Analysis of Differential Genes of Uyghur Women with Endometriosis in Xinjiang 361

**Description**

**ID Name Rate of** 

**Cy5/Cy3**

16687 TP73 1.277275 Tumor protein p73

22345 LOC440552 1.232367 similar to OK/SW-CL.16 8173 MARK2 1.227909 ELKL motif kinase

20299 IL1 RN 1.283803 Interleukin 1 receptor antagonist

21216 SLPI 1.215856 Secretory leukocyte protease inhibitor

19718 SULT1C2 1.207869 Sulfotransferase family, cytosolic, 1C,

22785 PDGFRA 1.159421 Platelet-derives growth factor receptor

12903 HSPA5BP1 1.179906 Hypothetical protein FLJ20539

8626 GPX3 1.078504 Glutathione peroxidase 3(plasma)

17362 FKBP14 1.036957 Hypothetical protein FLJ20731

21961 RPS23 1.025033 Ribosomal protein S23 1580 NELF 1.017617 DKFZP586J1624 protein

(Continuation)

20231 SERF2 1.112907 Small EDRK-rich factor 2 15491 ZNF14 1.104864 Zinc finger protein 14 (KOX 6) 9735 KIAA0635 1.100348 Hypothetical protein FLJ13621

16540 CDW92 1.092801 CDw92 antigen

22866 ACTB 1.083347 Actin, beta

mendometriosisber 2

1900 GNG5 1.125384 Guanine nucleotide binding protein (G protein), gamma 5

22762 COPEB 1.08944 Core promoterelendometriosisent binding protein

19581 GNG5 1.057676 Guanine nucleotide binding protein (G protein), gamma 5

1401 ELAVL3 1.077059 ELAV (endometriosisbryonic lethal,abnormal vision,

7186 ID3 1.057184 Inhibitor of DNA binding 3, dominant negative helixloop-helix protein

9824 MTBP 1.030879 Mdm2, transformed 3T3 cell double minute 2, p53

8364 ARHGDIA 1.029915 Rho GDP dissociation inhibitor (GDI) alpha

22665 GAPD -1.003765 Glyceraldehyde-3-phosphate dehydrogenase 22761 GAPD -1.001544 Glyceraldehyde-3-phosphate dehydrogenase 17133 GAPD -4.29046 Glyceraldehyde-3-phosphate dehydrogenase Table 2. Han with and without endometriosis ectopic endometriosis differential genes.

Drosophila)-like 3 (Hu antigen C)

binding protein (mouse) binding protein, 104kD

9988 ACTB 1.293784 Actin,beta

22986 ACTB 1.267406 Actin, beta 22770 ACTB 1.258614 Actin, beta 10599 VIM 1.251847 Vimentin 22865 ACTB 1.233357 Actin, beta

22962 ACTB 1.219306 Actin, beta

22690 ANKT 1.213863 Nucleolar protein 23200 LOC389622 1.212664 LOC389622 22961 ACTB 1.212137 Actin, beta 22673 ACTB 1.210056 Actin, beta 22890 ACTB 1.208872 Actin, beta


Table 2. Han with and without endometriosis ectopic endometriosis differential genes.

18428 FTL 4.340706 ESTs,Weakly similar to FRHUL ferritin light chain [H.sapiens]

20900 IGL@ 2.941947 H.sapiens mRNA for IgG lambda light chain V-J-C region (clone Tgl9)

10901 IGHG3 2.24961 Immunoglobulin heavy constant gamma 3 (G3m marker)

family,mendometriosisber 7A

7998 CD74 3.623251 CD74 antigen (invariant polypeptide of major

21034 CTSD 2.992721 Cathepsin D (lysosomal aspartyl protease)

16743 IGKV1-9 2.482954 Immunoglobulin kappa variable 1-9

15732 ACTA2 1.939791 Actin,alpha 2,smooth muscle,aorta 6876 HLA-G 1.795164 HLA-G histocompatibility antigen,class I,G 9464 HLA-A 1.617767 Major histocompatibility complex,class I,A 12611 ITM2C 1.60875 Integral mendometriosisbrane protein 3

6875 WNT7A 1.55996 Wingless-type MMTV integration site

13167 IGFBP7 1.486395 Insulin-like growth factor binding protein 7

12651 SPARC 1.441213 Secreted protein,acidic,cysteine-rich (osteonectin)

Table 2. Han with and without endometriosis ectopic endometriosis differential genes.

6494 FTH1 1.55145 Ferritin,heavy polypeptide 1

10474 FLJ14950 1.489821 Hypothetical protein FLJ14950

1.460991 Cw1 antigen

14701 HSU79274 1.391079 Protein predicted by clone 23733

5712 GPX3 1.370492 Glutathione peroxidase 3(plasma)

**Description**

histocompatibility complex,class II antigen-associated

**ID Name Rate of** 

**Cy5/Cy3**

8586 APOE 3.768085 Apolipoprotein E

18699 BIN3 3.235432 Bridging integrator 3

17716 ZFHXI B 2.221742 Zinc finger homeobox 1 b

9202 DLGAP4 1.56221 KIAA0964 protein

6952 TMSB10 1.539032 Thymosin,beta 10

22794 ACTB 1.51553 Actin,beta 22769 ACTB 1.495315 Actin,beta

22698 ACTB 1.45868 Actin,beta

22793 ACTB 1.374773 Actin,beta

22985 ACTB 1.342603 Actin,beta 22674 ACTB 1.333726 Actin,beta 22697 ACTB 1.33342 Actin,beta 21176 KPT13 1.327325 Keratin 13 22889 ACTB 1.325337 Actin,beta 22700 CYC1 1.325323 Cytochrome c-1 23193 LOC389643 1.323453 LOC389643

22696 RPL5 1.421712 Ribosomal protein L5 13180 LOC51237 1.416254 Hypothetical protein

18071 HUMMHC W1A

10633 CTSB 2.736133 Cathepsin B


Table 2. Han with and without endometriosis ectopic endometriosis differential genes. (Continuation)

Analysis of Differential Genes of Uyghur Women with Endometriosis in Xinjiang 363

screened out between Uyhgur women with or without endometriosis respectively, FOS, DCN, VIN, GNGS, XCL 1, IGFBP7, PRS23, TIMP3, COL3A1, PRL29, GAPD; GAPD expression in the three loci, including FOS, DCN, VIN, GNGS, XCL1, IGFBP7, PRS23 were up-regulated, and TIMP3, COL3A1, PRL29, GAPD were down-regulated. The Han chinese group were significantly different genes, 58 of which TIMP3, PAEP, GADP were downregulated, but GADP expressed in three loci shows different range. And from a different CD74, ACTA2, GPX3 and other 55 genes were upregulated, ACTB appear in 17 loci, GNGS appear in two loci. The same genes difference between the two groups is VIM, GNGS, PRS23, GAPD, TIMP3, including GAPD, TIMP3 are down-regulated. We get different genes according to their main function and are divided into the following categories: immunerelated genes,proto-oncogenes and tumor suppressor genes,cell receptor,ion channels and transport protein; cytoskeleton and sports-related protein, apoptosis-related protein; DNA synthesis and repair, recombinant protein, DNA binding, transcription and transcription

factors,cell signaling and transmission white and some unknown functional genes.

**pathogenesis** 

compared with the ectopic endometrium.

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

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,

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,


Table 2. Han with and without endometriosis ectopic endometriosis differential genes. (Continuation)
