Thalidomide Reduces Cell Proliferation in Endometriosis Experimentally Induced in Rats

Abstract

Objective To analyze the effect of thalidomide on the progression of endometriotic lesions experimentally induced in rats and to characterize the pattern of cell proliferation by immunohistochemical Proliferating Cell Nuclear Antigen (PCNA) labeling of eutopic and ectopic endometrium. Methods Fifteen female Wistar rats underwent laparotomy for endometriosis induction by resection of one uterine horn, isolation of the endometrium and fixation of a tissue segment to the pelvic peritoneum. Four weeks after, the animals were divided into 3 groups: control (I), 10mg/kg/day (II) and 1mg/kg/day (III) intraperitoneal thalidomide for 10 days. The lesion was excised together with the opposite uterine horn for endometrial gland and stroma analysis. Eutopic and ectopic endometrial tissue was submitted to immunohistochemistry for analysis of cell proliferation by PCNA labeling and the cell proliferation index (CPI) was calculated as the number of labeled cells per 1,000 cells. Results Group I showed a mean CPI of 0.248 ± 0.0513 in the gland and of 0.178 ± 0.046 in the stroma. In contrast, Groups II and III showed a significantly lower CPI, that is, 0.088 ± 0.009 and 0.080 ± 0.021 for the gland (p < 0.001) and 0.0945 ± 0.0066 and 0.075 ± 0.018 for the stroma (p < 0.001), respectively. Also, the mean lesion area of Group I was 69.2 mm2, a significantly higher value compared with Group II (49.4 mm2, p = 0.023) and Group III (48.6 mm2, p = 0.006). No significant difference was observed between Groups II and III. Conclusion Thalidomide proved to be effective in reducing the lesion area and CPI of the experimental endometriosis implants both at the dose of 1 mg/kg/day and at the dose of 10 mg/kg/day.

Approach to Pain in Endometriosis Patients: Systematic Literature Review

“…However, further studies are needed to fully understand the molecular mechanisms that justify resistance to these drugs. Furthermore, thalidomide, a drug that acts on cell proliferation without interfering with ovarian function, has been shown to reduce the size of cysts in the retrocervical and ovarian regions, as well as decrease pelvic pain, in women with endometriosis [39].…”

Talidomida no manejo da dor em endometriose: uma revisão de escopo de estudos experimentais

“…It is also observed that there is an increase in angiogenic activity in the region of the lesion, which intensifies the inflammatory effect due to the greater disposition of factors coming from the circulation. The sum of the two effects, stimulated in the long term, develops the chronic form of endometriosis, which makes treatment difficult 5 .…”

Autoimmune Disease-Related Hub Genes are Potential Biomarkers and Associated with Immune Microenvironment in Endometriosis

“…These are primarily determined by the typical clinical manifestations and associated examination diagnosis It has been demonstrated in animal models that immunosuppressants such as thalidomide and triptolide, as well as biological agents such as etanercept and infliximab, are beneficial in reducing the size of ectopic lesions and EMT in the treatment of autoimmune disorders. 34,35 Through this study, we screened out the AIDGs hub genes related to EMT, CXCL12, PECAM1, NGF, CTGF, and WNT5A, and analyzed the diagnostic value of hub genes and the correlation with immune microenvironment. First, by analyzing the immune microenvironment of the EU and EC endometrium, it was found that macrophages, mast cells and T cells CD4 memory quiescent in the EC endometrium had a high percentage, while NK cells and plasma cells accounted for a relatively small percentage.…”