Effect of aromatase inhibitors on ectopic endometrial growth and peritoneal environment in a mouse model of endometriosis Mariela Bilotas, Ph.D., Gabriela.

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Effect of aromatase inhibitors on ectopic endometrial growth and peritoneal environment in a mouse model of endometriosis Mariela Bilotas, Ph.D., Gabriela Meresman, Ph.D., Inés Stella, M.D., Carlos Sueldo, M.D., Rosa Inés Barañao, Ph.D. Fertility and Sterility Volume 93, Issue 8, Pages 2513-2518 (May 2010) DOI: 10.1016/j.fertnstert.2009.08.058 Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Aromatase expression in endometriosis-like lesions. Endometriosis-like lesions from control mice were dissected away, formalin fixed, paraffin embedded, and cut into sections. Aromatase expression was evaluated by immunohistochemistry using a polyclonal antibody. Low (A and B) and high (C and D) aromatase expression was seen in mouse ectopic endometrium. Mouse ovary sections were used as positive control (E). In negative control (F) immunoglobulin of the same immunoglobulin class and concentration as the primary antibody was used. Magnification, ×100 (A, C, and E); ×400 (B, D, and F). Fertility and Sterility 2010 93, 2513-2518DOI: (10.1016/j.fertnstert.2009.08.058) Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions

Figure 2 Effect of aromatase inhibitors on endometriotic lesion size. Mice with surgically induced endometriosis were treated either with anastrozole, letrozole, or saline (control) starting on postoperative day 1 (A) or 28 (B). After 4 weeks of treatment mice were sacrificed and endometriotic lesions were measured. ∗P<.05 vs. control; ∗∗∗P<.001 vs. control. Fertility and Sterility 2010 93, 2513-2518DOI: (10.1016/j.fertnstert.2009.08.058) Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions

Figure 3 Effect of aromatase inhibitors on epithelial cell proliferation (PCNA+) (A) and apoptosis (B) of ectopic uterine tissue. Mice with surgically induced endometriosis were treated either with anastrozole, letrozole, or saline (control) starting on postoperative day 1 or 28. After 4 weeks of treatment mice were sacrificed and endometriosis-like lesions were dissected away, formalin fixed, paraffin embedded, and cut into sections. Cell proliferation (A) was evaluated by immunohistochemistry for PCNA and apoptosis (B) was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP digoxygenin nick-end labeling (TUNEL). ∗P<.05 vs. control; ∗∗P<.01 vs. control; ∗∗∗P<.001 vs. control. Fertility and Sterility 2010 93, 2513-2518DOI: (10.1016/j.fertnstert.2009.08.058) Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions

Figure 4 Effect of aromatase inhibitors on vascular endothelial growth factor (VEGF) (A) and prostaglandin E (PGE) (B) levels in peritoneal fluid (PF). Mice with surgically induced endometriosis were treated either with anastrozole, letrozole, or saline (control) starting on postoperative day 28. After 4 weeks of treatment mice were sacrificed and the PF was collected. The levels of VEGF (A) were assessed by ELISA and the levels of PGE (B) were determined by RIA. ∗P<.05 vs. control; ∗∗∗P<.001 vs. control. Fertility and Sterility 2010 93, 2513-2518DOI: (10.1016/j.fertnstert.2009.08.058) Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions