Evaluation of the potential therapeutic effects of a double-stranded RNA mimic complexed with polycations in an experimental mouse model of endometriosis

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Presentation transcript:

Evaluation of the potential therapeutic effects of a double-stranded RNA mimic complexed with polycations in an experimental mouse model of endometriosis Carmen Maria García-Pascual, Ph.D., Jessica Martínez, Ph.D., Paula Calvo, M.D., Hortensia Ferrero, Ph.D., Ana Villanueva, Ph.D., Mercedes Pozuelo-Rubio, Ph.D., Marisol Soengas, Ph.D., Damiá Tormo, Ph.D., Carlos Simón, M.D., Antonio Pellicer, M.D., Raúl Gómez, Ph.D. Fertility and Sterility Volume 104, Issue 5, Pages 1310-1318 (November 2015) DOI: 10.1016/j.fertnstert.2015.07.1147 Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

Figure 1 In vivo imaging of endometriotic implants in control, anti-VEGF, and pICPEI treated animals. (A) Examples of the fluorescence signaling provided by mCherry-labeled endometriotic implants in animals monitored during a 4-week time course. (B) Quantitative analysis of mean ± SEM fluorescence intensity provided by implants in the three groups during the time course. *P<.05 anti-VEGF vs. control group. Fertility and Sterility 2015 104, 1310-1318DOI: (10.1016/j.fertnstert.2015.07.1147) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

Figure 2 The effect of pICPEI on macroscopic features of human endometrial implants on the peritoneal wall of mice administered with (A, B) vehicle, (C, D) pICPEI, and (E, F) the anti-VEGF compound CBO-P11 at the end of the 4-week treatment period. Scale bars = 8 mm. Fertility and Sterility 2015 104, 1310-1318DOI: (10.1016/j.fertnstert.2015.07.1147) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

Figure 3 Effect of pICPEI on vascularization of endometriotic implants. (A) Immunofluorescent staining pattern for PECAM (a vascularization marker, staining in green) and α-SMA (a muscular layer marker of mature vessels, staining in red) in endometriotic implants obtained after killing the mice treated with control, anti-VEGF, or pICPEI. Mature vessels are identified by overlapping yellow color. Scale bar = 150 μm. (B) Vascularization as represented by the percentage of PECAM staining (green) vs. total area. (C) Percentage of immature vessels as represented by the number of immature, not surrounded by a red muscular layer, vessels (PECAM+/α-SMA−) divided by the total number of vessels (PECAM+). *P<.05 vs. control group. Fertility and Sterility 2015 104, 1310-1318DOI: (10.1016/j.fertnstert.2015.07.1147) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

Figure 4 Effect of pICPEI treatment on cell proliferation and apoptosis of endometriotic implants. (A) Proliferating cells stained against the proliferation marker Ki67 (red color) and (B) apoptotic cells recognized by labeling DNA breaks induced by DNAse I (red color) in endometriotic implants obtained after killing the control, anti-VEGF, and pICPEI treated mice. Scale bar = 150 μm. (C) Cellular proliferation and (D) apoptosis among the three groups (mean + SEM). *P<.05 vs. control group. Fertility and Sterility 2015 104, 1310-1318DOI: (10.1016/j.fertnstert.2015.07.1147) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions