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Problem: To evaluate the effects of SR-16234 (SR), a selective estrogen receptor modulator (SERM), on murine endometriosis-like lesions., Method of Study: BALB/c mice (n = 53) were used to establish the murine endometriosis model. Ovariectomized, estradiol replaced, 6-week-old murine endometriosis model were injected with lipopolysaccharide (LPS) with or without SR (1 mg/kg/d) or vehicle, over a period of 4 weeks. Upon treatment completion, the endometriosis-like lesions that developed in the abdominal cavity of mice were counted, measured, and collected. Gene expression of inflammatory cytokines and estrogen receptor (ER) in the lesions was assessed by real-time RT-PCR. Immunohistochemical analysis was used to evaluate the effect of SR on cell proliferation, angiogenic activity, inflammation, and NF-κB phosphorylation., Results: Treatment with SR significantly reduced the total number and size of lesions per mouse without inducing endometrial growth. In addition, SR downregulated LPS-enhanced Vegf, Il-6, Ptgs-2, and Ccl-2 and ER mRNA expression in endometriosis-like lesions. Immunohistochemical analysis demonstrated a decrease in percentage of positive cells of Ki67, and intensity and rate of positive cells of ERα, CD3, F4/80, PECAM by SR treatment. SR also decreased the expression of NF-κB p65 and phospho-NF-κB p65., Conclusion: SR has a regressive effect on the development of murine endometriosis-like lesions., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Problem: How is the role of inhibitor of apoptosis proteins (IAPs) in the development of murine endometriosis lesions?, Method of Study: BALB/c female mice (n = 36) were used for the murine endometriosis model. Endometriotic lesions were surgically induced in mice by transplanting mouse uterine tissue. After 4 weeks of IAP antagonist (BV6) treatment, the expression of inflammatory factors in the implants was evaluated using real-time RT-PCR. Inflammatory state, angiogenic activity, and nuclear factor-kappa B (NF-κB) activation were assessed by immunohistochemical staining., Results: The number, size, and level of inflammatory cytokines (Vegf, Il-6, Ccl-2, Lif) gene expression in the murine endometriosis-like lesions were reduced by BV6 treatment. BV6 repressed the intensity and rate of positive cells of CD3, F4/80, and PECAM immunostaining; in addition, the expression of NF-κB p65 and phospho-NF-κB p65 was also attenuated., Conclusion: Inhibitor of apoptosis proteins antagonist represses the inflammation status of murine endometriosis-like lesions viaNF-κB pathway. IAPs may be a novel therapeutic target for endometriosis., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the effects of parthenolide on human endometriotic cells and murine endometriotic lesions., Design: Experimental study., Setting: University hospital and laboratory of animal science., Patient(s) and Animal(s): Twenty women with ovarian endometrioma and 30 mice., Intervention(s): Ectopic endometrial tissue from the endometrioma was collected., Main Outcome Measure(s): Human endometriotic stromal cells (ESCs) were pretreated with parthenolide and exposed to tumor necrosis factor (TNF)-α. Interleukin 8 (IL-8) and COX-2 gene expressions were evaluated by real-time reverse transcription-polymerase chain reaction. Interleukin-8 protein, prostaglandin E₂ (PGE₂) level, and intranuclear p65 protein concentration were determined by ELISA. Cell proliferation was assessed by 5-bromo-2'-deoxyuridine-ELISA. Phosphorylation of signaling pathways in ESCs was evaluated by Western blotting. Gene expression and proliferative activity in murine endometriosis-like lesions were assessed by real-time reverse transcription-polymerase chain reaction and Ki67 staining, respectively., Result(s): With parthenolide pretreatment, TNF-α-induced IL-8 gene and protein expression in ESCs were diminished. Tumor necrosis factor α-induced COX-2 expression and PGE2 synthesis were also inhibited. Adding parthenolide repressed TNF-α-induced 5-bromo-2'-deoxyuridine incorporation and IκB phosphorylation in ESCs. As in vivo experiments, administering parthenolide reduced the number, surface area, and weight, the level of Vegf, Il-6, Mcp-1, and Lif gene expression, and the percentage of Ki67-positive cells in murine endometriosis-like lesions., Conclusion(s): Parthenolide repressed the development of endometriosis by suppressing the inflammatory peritoneal environment through the nuclear factor κB pathway., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Problem: How are the effects of Tokishakuyakusan (TSS), a traditional Japanese medicine (Kampo) on murine endometriosis model? Methods: BALB/c mice were used for making the murine endometriosis model. Homogeneous uterus was surgically implanted with lipopolysaccharide (LPS) in peritoneal cavity. We administered 2 weeks of TSS (1.0 g/kg) orally. Upon treatment completion, we performed the hot plate test for all mice and collected blood samples before sacrifice. Then, the endometriosis‐like lesions and uteri in the abdominal cavity were harvested. Concentrations of several cytokines in sera and cyst fluids were measured using Bio‐Plex Suspension Array System. IL‐33 localization was determined by immunohistochemistry. Gene expression of inflammatory cytokines in the endometriosis‐like lesions or the eutopic endometrium was evaluated by real‐time RT‐PCR. Results: After 14 days of TSS treatment, the numbers of endometriosis‐like cysts and cyst weight were significantly decreased. In TSS‐treated mice, the latency against heat stimuli was extended. Inflammatory cytokine concentrations in sera were not changed by TSS treatment. TSS intake decreased IL‐33 mRNA expression in endometriosis‐like lesions and led to the tendency of attenuation of the elevated IL‐33 synthesis in the cyst fluids of lesions. Conclusion: These results suggest the TSS ameliorated the hyperalgesia and lesion formation on the LPS‐accelerated endometriosis‐like model. TSS represents a possible ideal target of novel therapeutics for endometriosis patients with dysmenorrhea. [ABSTRACT FROM AUTHOR]