1. Nonsteroidal antiinflammatory drugs differentially suppress endometriosis in a murine model 
Jason A. Efstathiou, M.D., David A. Sampson, B.A., Zalman Levine, M.D., Richard M. Rohan, Ph.D., David Zurakowski, Ph.D., Judah Folkman, M.D., Robert J. D'Amato, M.D., Maria A. Rupnick, M.D., Ph.D. 
Fertility and Sterility 
Volume 83, Issue 1, Pages (January 2005)
DOI: /j.fertnstert
Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

2. FIGURE 1
(A, B) Gross and (C, D) histologic comparisons of endometriotic lesions between the murine model and the human disease. Vascularized lesions with fluid-filled cysts characterize the murine model (A, arrow) and resemble those seen clinically via laparoscopic imaging (B, arrow). The murine lesions (C) also share histologic hallmarks of the human pathology (D), such as endometrial glands and stroma, fluid-filled cysts lined by epithelial cells, and hemosiderin. Both are also highly vascularized as illustrated by endothelial cell staining (CD31, brown vessels).
Fertility and Sterility  , DOI: ( /j.fertnstert )
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3. FIGURE 2
Endometrial implants assessed at the conclusion of the studies. (A) Established endometriotic lesion consisting of endometrial tissue and cysts from a control animal. (B) Nonestablished lesions with no measurable endometriotic tissue detectable at the sutures that mark the implantation site. These lesions were photographed from an animal treated with celecoxib for 4 weeks.
Fertility and Sterility  , DOI: ( /j.fertnstert )
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4. FIGURE 3
The effect of NSAIDs on endometriosis in the murine model was assessed based on (A) lesion establishment (the percent of the implanted lesions that were measurable at the conclusion of the study); (B) lesion growth (the mean size of only the established lesions in each animal); and (C) total lesion burden (mean size of all seven implants, established and nonestablished). NSAIDs significantly and differentially suppressed the establishment and progression of endometriosis in this model. The number of animals for each group are: control, n = 29; aspirin, n = 7; celecoxib, n = 16; ibuprofen, n = 16; indomethacin, n = 8; naproxen, n = 8; sulindac, n = 7; and rofecoxib, n = 14. *P<.05, **P<.001, ***P<.0001.
Fertility and Sterility  , DOI: ( /j.fertnstert )
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5. FIGURE 4
Celecoxib did not affect established lesions. Treatment was initiated on postoperative day 1, 15, or 30 and continued for 4 weeks. Disease burden was reduced when treatment was initiated before lesion establishment on postoperative day 1 (***P<.001). However, there was no statistically significant difference between disease burdens when treatment was delayed until postoperative days 15 or 30 compared with the respective controls. This indicates that celecoxib had no effect on established lesions. The number of animals for each group are: day-1 control, n = 8; day-1 celecoxib, n = 8; day-15 control, n = 7; day-15 celecoxib, n = 8; day-30 control, n = 7; day-30 control, n = 7.
Fertility and Sterility  , DOI: ( /j.fertnstert )
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6. FIGURE 5
Celecoxib significantly and similarly reduced the disease burden of endometriosis in the murine model in the presence of physiologic and supraphysiologic estrogen levels. The number of animals for each group are: cycling control, n = 8; cycling celecoxib, n = 8; exogenous E2 control, n = 9; exogenous E2 celecoxib, n = 9. ***P<.0001.
Fertility and Sterility  , DOI: ( /j.fertnstert )
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7. FIGURE 6
The disease burden in the celecoxib-treated mice was statistically significantly less than that of controls when assessed at the conclusion of the 4-week treatment period (*P <.05). However, a month following discontinuation of the treatment, there was no statistically significant difference between the groups. This reflects an increase in the disease burden in the mice previously treated with celecoxib. The number of animals in each group are: lesions assessed at end of treatment, n = 3 each for control and celecoxib; lesions assessed at 4 weeks after treatment, n = 8 each for control and celecoxib.
Fertility and Sterility  , DOI: ( /j.fertnstert )
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8. FIGURE 7
Vessel density was not statistically significantly different in endometriotic lesions in control mice or in mice treated with celecoxib or aspirin. Vessels were identified using CD31 staining of vascular endothelium and quantified as percentage area using an image analysis system. There are five animals in each group.
Fertility and Sterility  , DOI: ( /j.fertnstert )
Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions