Qiong-Hua Chen, Ph. D. , Wei-Dong Zhou, Ph. D. , De-Min Pu, M. D

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15-Epi-lipoxin A4 inhibits the progression of endometriosis in a murine model Qiong-Hua Chen, Ph.D., Wei-Dong Zhou, Ph.D., De-Min Pu, M.D., Qian-Sheng Huang, Ph.D., Tian Li, Ph.D., Qing-Xi Chen, Ph.D. Fertility and Sterility Volume 93, Issue 5, Pages 1440-1447 (March 2010) DOI: 10.1016/j.fertnstert.2009.01.107 Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Inhibitory effect of LXA4 on the progression of the endometriotic lesions in mice (A) EM group, (B) LXA4-treated group, (C) histopathologic examination. Fertility and Sterility 2010 93, 1440-1447DOI: (10.1016/j.fertnstert.2009.01.107) Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions

Figure 2 Loss of the total weight of endometriotic lesions in LXA4 group. The mice in the LXA4 group were treated with LXA4 5 μg/kg, every 8 hours, starting 3 days before the EM induction, for 24 days, whereas the controls were treated with vehicles. Horizontal bars represent the means of each group. Fertility and Sterility 2010 93, 1440-1447DOI: (10.1016/j.fertnstert.2009.01.107) Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions

Figure 3 No effect of estrous cycling in LXA4 group. Methylene blue-stained vaginal smears at different stages of the estrous cycle: (A) diestrus, (B) proestrus, (C) estrus, (D) metestrus). Magnification, ×400. (E) The dots represent the number of mice that went through different lengths of estrous cycle over a period of 24 days as determined by daily vaginal smear. Fertility and Sterility 2010 93, 1440-1447DOI: (10.1016/j.fertnstert.2009.01.107) Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions

Figure 4 Concentrations of MMP-2 and MMP-9 in peritoneal fluids measured by ELISA. The mean levels of MMP-2 and MMP-9 were significantly reduced in peritoneal fluids of LXA4 mice compared with those in the EM group, which were significantly higher than those in sham-operated group. Error bars indicate SD. ∗P<.05, ∗∗P<.01, EM versus Sham; +P<.05, ++P<.01, LXA4 versus EM. Fertility and Sterility 2010 93, 1440-1447DOI: (10.1016/j.fertnstert.2009.01.107) Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions

Figure 5 (A) MMP-2 mRNA and MMP-9 mRNA expression in peritoneal cavity cells. The levels of MMP-2 mRNA and MMP-9 mRNA in peritoneal cavity cells were significantly lower in the LXA4 group than those in the EM group, which were significantly higher than those in the sham-operated group. Error bars indicate SD. ∗P<.05, ∗∗P<.01, EM versus sham; +P<.05, ++P<.01, LXA4 versus EM. (B) MMP-2 mRNA expression in ectopic and eutopic endometria. The levels of MMP-2 mRNA in both ectopic and eutopic endometrial in the LXA4 group were significantly lower than those in the EM group, which were significantly higher than the those in the sham-operated group. Error bars indicate SD. ∗P<.05, ∗∗P<.01, EM versus sham; +P<.05, ++P<.01, LXA4 versus EM. (C) MMP-9 mRNA expression in ectopic and eutopic endometria. The levels of MMP-9 mRNA in both ectopic and eutopic endometria in the LXA4 group were significantly lower than those in the EM group, which were significantly higher than those in the sham-operated group. Error bars indicate SD. ∗P<.05, ∗∗P<.01, EM versus sham; +P<.05, ++P<.01, LXA4 versus EM. Fertility and Sterility 2010 93, 1440-1447DOI: (10.1016/j.fertnstert.2009.01.107) Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions

Figure 6 Inhibitory effect of LXA4 on the activities of MMP-2 and MMP-9. (A) MMP-2 and MMP-9 proteins detected by gelatin-substrate zymography on the basis of their gelatinolytic activity and molecular masses (proenzyme and active forms). (B) Densitometric analysis. The relative enzymatic activities of MMP-2 and MMP-9 in peritoneal fluid in LXA4 group were significantly reduced compared with those in EM group, which were significantly higher than those in the sham-operated group. Fertility and Sterility 2010 93, 1440-1447DOI: (10.1016/j.fertnstert.2009.01.107) Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions