Hum. Reprod. Advance Access originally published online on November 26, 2004
Human Reproduction 2005 20(2):350-358; doi:10.1093/humrep/deh611
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Nimesulide, a COX-2 inhibitor, does not reduce lesion size or number in a nude mouse model of endometriosis
1 Reproductive Molecular Research Group, Department of Pathology Tennis Court Road, Cambridge CB2 1QP, 2 University Department of Obstetrics and Gynaecology, The Rosie Hospital, Robinson Way, Cambridge CB2 2SW and 3 Discovery Biology, Pfizer Global Research and Development, Sandwich, Kent, UK
4 To whom correspondence should be addressed. Email: mlh30{at}cam.ac.uk
BACKGROUND: Women with endometriosis have elevated levels of cyclooxygenase-2 (COX-2) in peritoneal macrophages and endometriotic tissue. Inhibition of COX-2 has been shown to reduce inflammation, angiogenesis and cellular proliferation. It may also downregulate aromatase activity in ectopic endometrial lesions. Ectopic endometrial establishment and growth are therefore likely to be suppressed in the presence of COX-2 inhibitors. We hypothesized that COX-2 inhibition would reduce the size and number of ectopic human endometrial lesions in a nude mouse model of endometriosis. METHODS: The selective COX-2 inhibitor, nimesulide, was administered to estrogen-supplemented nude mice implanted with human endometrial tissue. Ten days after implantation, the number and size of ectopic endometrial lesions were evaluated and compared with lesions from a control group. Immunohistochemical assessment of vascular development and macrophage and myofibroblast infiltration in control and treated lesions was performed. RESULTS: There was no difference in the number or size of ectopic endometrial lesions in control and nimesulide-treated nude mice. Nimesulide did not induce a visually identifiable difference in blood vessel development or macrophage or myofibroblast infiltration in nude mouse explants. CONCLUSION: The hypothesized biological properties of COX-2 inhibition did not influence lesion number or size in the nude mouse model of endometriosis.
Key words: COX-2 inhibitor/endometriosis/mouse model/nimesulide/prostaglandin
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