New insights into the efficacy of SR-16234, a selective estrogen receptor modulator, on the growth of murine endometriosis-like lesions

Khine YM, Yin Mon Khine, Fuminori Taniguchi, Kei Nagira, Nagira K, Nakamura K, Kazuomi Nakamura, Ohbayashi T, Tetsuya Ohbayashi, Osaki M, Mitsuhiko Osaki, Tasuku Harada, Harada T
American journal of reproductive immunology (New York, N.Y. : 1989) · 2018 · vol. 80(5) , pp. e13023 · doi:10.1111/aji.13023 · PMID:30010222 · W2883864598
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SR-16234 treatment reduced the number and size of endometriosis-like lesions in mice by downregulating inflammatory, angiogenic, and ER gene expression and inhibiting NF-κB phosphorylation.

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Abstract

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.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometrium Interleukin-6 NF-kappa B Vascular Endothelial Growth Factor A Animals Animals Cell Growth Processes Cell Growth Processes Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Cyclooxygenase 1 Cyclooxygenase 1 Cyclooxygenase 1 Disease Models, Animal Disease Models, Animal Endometriosis Endometriosis Endometrium

Funding

funders
[{'doi': '10.13039/501100001691', 'name': 'Japan Society for the Promotion of Science', 'awards': ['26462490']}, {'doi': '10.13039/501100001691', 'name': 'Japan Society for the Promotion of Science', 'awards': ['15K10671']}]

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References (82)

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