**4.3 Endometriosis infertility protein detection**

Previous result of our group indicated [95] that 76 eutopic endometrial polyps cases of endometriosis group histologically resembled endometrial polyps but the majority of endometrial polyps with endometriosis occurred in primary infertility cases and in fewer pregnancy rate women who had stable and smaller EPs without association with the AFS stage. The recurrence rate of endometrial polyps with endometriosis group was higher than that in non endometriosis group. In 2009, Ferrero et al. [96] reported the peritoneal fluid proteome collected under laparoscopy from 26 fertile women and 26 infertile ones With endometriosis. One isoform of immunoglobulin light chain spot and 9 protein spots had been found significantly higher expression in PF of infertile patients than infertile controls by applied with

**31**

**Acknowledgements**

China (No. 30762222, No. 81170550).

*Proteomics Research and Its Possibility of Application in Endometriosis*

**4.4 Proteomics detection of animal models of endometriosis**

2-dimensional gel electrophoresis (2-DE) with computerized analysis and protein spots were identified by liquid chromatography tandem mass spectrometry (MS). No protein spots had significantly lower expression and 3 protein spots remain

Many animals such as rhesus monkeys, rabbits, and nude mice have been used as models for studying endometriosis, but most of these animals have no menstrual cycle, and only primates can spontaneously produce endometriosis with regular menstrual cycles and menstrual blood flow. Their pathogenesis and pathological features are similar to those of humans. Monkey experiments have confirmed that current menstrual bleeding can cause pelvic lesions. In 1991, Sharpe et al. [97] first reported using two-dimensional electrophoresis (2-DE) to observe that surgically induced ectopic endometrium in rats lacked progesterone-induced secretory uterin protein 21 (PUP21, MW 70 kDa, p I 5. 7), whereas normal endometrium expression of the protein suggests that PUP21 deficiency is associated with reduced fertility in patients with endometriosis. In 1993, Sharpe et al. [98] also used twodimensional electrophoresis to study the rat endometriosis implanted by surgery. It was found that ectopic endometrium specifically expressed two groups of proteins: ENDO I (MW 40–50 kDa, p I 4. 0–5. 2) and ENDO II (MW 28–32 kDa, p I 7.5–9.0). Further studies using amino acid sequence analysis confirmed that ENDO-2 is TIMP-1 and ENDO-1 is haptoglobin-like. Studies have shown that endometriotic lesions secrete haptoglobin in combination with macrophages to reduce their adherent phagocytic capacity, so that intimal ectopic cells cannot be eliminated, but haptoglobin can stimulate macrophages to secrete inflammatory cytokines such as IL-1, − 6 and TNF, IL-6 can up-regulate ectopic endometrium cells to express haptoglobin, forming a positive feedback in the lesion, thereby promoting the progression of endometriosis. In the peritoneal fluid and serum of patients with endometriosis, the concentration of TIMP-1 was significantly reduced. Therefore, the abnormal expression of TIMP-1 may be one of the causes of the onset of endo-

metriosis, and may become a potential marker for diagnosing this disease.

will undoubtedly bring about a new endometriosis diagnosis field.

Once we have discovered one or more proteins that are specifically expressed in patients with endometriosis, the next step is to develop them as a diagnostic test for it. The diagnostic method must have good sensitivity, specificity, positive predictive value, and negative predictive value. What we need to overcome is not only the individual differences in the population, but also the differences in specific tissue protein components and the effects of natural menstrual cycles or hormone effects. Protein chip, protein array mass spectrometry technique have been used to perform a comprehensive search of protein expression profiles of endometriosis patients in order to find a group of proteins with high sensitivity and specificity. Applying the changes in the expression of this group of proteins to diagnose and predict disease

This chapter was co-funded by the National Natural Science Foundation of

**5. Possible directions in the future**

*DOI: http://dx.doi.org/10.5772/intechopen.81850*

unidentified.

*Molecular Bases of Endometriosis - The Integration Between Research and Clinical Practice*

ATP synthase may play an important role in ectopic endometrium as it needs invasive, and cell adhesion and cytoskeletal remodeling. Vimentin and β-actin is a cytoskeletal protein. Studies have shown that the expression of these proteins is upregulated in the endometrium in patients with endometriosis. These proteins have a certain effect on the formation of endometriotic lesions. Given that the occurrence of endometriosis may be due to an abnormality of eutopic endometrium itself. In 2007 and 2008, Liang [93] and others used surface-enhanced laser desorption/ ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology to study serum protein expression in patients with endometriosis and healthy controls. A diagnostic model consisting of 5 protein peaks was established with a sensitivity of 91.7% and a specificity of 90.0% provides new prospect for screening endometriosis markers. In 2007, Liu et al. [90] also used SELDI-TOF-MS technology to study plasma protein expression in patients with endometriosis and healthy controls. It was found that 20 protein peaks were elevated or decreased in both of them. The

**4.2 Expression and significance of tissue protein in patients with Endometriosis**

Previous result of our group indicated [95] that 76 eutopic endometrial polyps cases of endometriosis group histologically resembled endometrial polyps but the majority of endometrial polyps with endometriosis occurred in primary infertility cases and in fewer pregnancy rate women who had stable and smaller EPs without association with the AFS stage. The recurrence rate of endometrial polyps with endometriosis group was higher than that in non endometriosis group. In 2009, Ferrero et al. [96] reported the peritoneal fluid proteome collected under laparoscopy from 26 fertile women and 26 infertile ones With endometriosis. One isoform of immunoglobulin light chain spot and 9 protein spots had been found significantly higher expression in PF of infertile patients than infertile controls by applied with

In 2006, Kyama et al. [5] used SELD I-TOF-MS technology to find that the expression of proteins and peptides in the eutopic endometrium of patients with endometriosis weight range of 2.8–12.3 kDa was 3–24 times lower than the molecular with non endometriosis. The expression of proteins and peptides in the lesions of patients with endometriosis had a tendency to increase within the molecular weight range of 3–96 kDa, and especially an up-regulated cluster of proteins between 22 and 23 kDa, identified to be transgelin, a smooth muscle actin-binding protein. In 2007 Fowler et al. [94] used 2-DE and peptide mass (MS) technology to confirm that the protein associated with endometriosis. Several deregulated proteins are identified: (1) chaperones and calcium binding proteins include heat shock protein 90 (HSP90) and annexin A2. (2) Cell oxygenation status related to protein, such as peroxiredoxin and thioredoxin-1, -2 (thioredoxin reductase-1, -). (3) Proteins associated with protein/DNA synthesis/decomposition, such as nucleoside diphosphate reductase, prohibitin, and proline-4-hydroxylase. (4) Secreted proteins, such as apolipoprotein A1. (5) Structural proteins such as vimentin and actin, whose function suggests that they play a role in the pathogenesis of endometriosis. At the same time, it was believed that the differentially expressed protein spots produced are identical whether the lysate of the endometrium was aggregated or isolated. Immunohistochemistry, Western blotting, and biological effects were also used to validate differential proteins and achieve desirable results. This study demonstrated that 2-DE gel analysis and mass spectroscopic protein identification are suitable for the identification of proteins with candidate associations with endometriosis.

sensitivity was 87.5% and the specificity was 80.0%.

**4.3 Endometriosis infertility protein detection**

**30**

2-dimensional gel electrophoresis (2-DE) with computerized analysis and protein spots were identified by liquid chromatography tandem mass spectrometry (MS). No protein spots had significantly lower expression and 3 protein spots remain unidentified.
