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

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