Reduced expression of progesterone receptor-B in the endometrium of women with endometriosis and in cocultures of endometrial cells exposed to 2,3,7,8-

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Reduced expression of progesterone receptor-B in the endometrium of women with endometriosis and in cocultures of endometrial cells exposed to 2,3,7,8- tetrachlorodibenzo-p-dioxin Toshio M. Igarashi, M.D., Ph.D., Kaylon L. Bruner-Tran, Ph.D., Grant R. Yeaman, Ph.D., Bruce A. Lessey, M.D., Ph.D., Dean P. Edwards, Ph.D., Esther Eisenberg, M.D., Kevin G. Osteen, Ph.D. Fertility and Sterility Volume 84, Issue 1, Pages 67-74 (July 2005) DOI: 10.1016/j.fertnstert.2005.01.113 Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 1 The PR-B/PR-A ratio in endometrial tissue in vivo: box plot of endometrial PR-B/PR-A ratio during the proliferative phase of healthy women and endometriosis patients. Densitometric analysis of Western blots was performed to determine the PR-B/PR-A ratio in extracts of whole endometrium. Center lines indicate the median ratio. Columns and vertical bars indicate the 25–75 percentiles and 10–90 percentiles, respectively. (Mann-Whitney U test; U = 32, P=.0019.) Igarashi. TCDD and PR-B:PR-A in endometriosis. Fertil Steril 2005. Fertility and Sterility 2005 84, 67-74DOI: (10.1016/j.fertnstert.2005.01.113) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 2 (A) Impact of TCDD (0.0–20.0 nM) on the expression and regulation of PR-A (94 kd) and PR-B (116 kd) protein in normal endometrial stromal cells cocultured with normal endometrial epithelial cells. Nonane, the diluent for TCDD, slightly stimulated PR expression. Relative intensity of each band was determined by densitometry and is graphically illustrated. (B) RT-PCR of total RNA extracted from normal endometrial stromal cells cocultured with normal endometrial epithelial cells and treated in vitro with TCDD or nonane using probes specific for PR-B or amplifying both PR-A and PR-B. Relative intensity of each band was determined by densitometry and is graphically illustrated. All experiments were repeated at least three times, and the results of a representative experiment are shown. Igarashi. TCDD and PR-B:PR-A in endometriosis. Fertil Steril 2005. Fertility and Sterility 2005 84, 67-74DOI: (10.1016/j.fertnstert.2005.01.113) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 3 MMP expression and regulation in cocultures of proliferative phase endometrial stromal and epithelial cells from a woman without endometriosis. (A) The presence of pro-MMP-7 and pro-MMP-3 was determined by Western analysis of conditioned media following 5 to 6 days in culture. Cells were treated with 1 nM estradiol (E) or 1 nM estradiol plus 500 nM progesterone (EP) with or without 10 nM TCDD. (B) All blots were stripped and probed for β-actin, a housekeeping protein, and subjected to densitometric analysis. All experiments were repeated at least three times, and the results of a representative experiment are shown. Igarashi. TCDD and PR-B:PR-A in endometriosis. Fertil Steril 2005. Fertility and Sterility 2005 84, 67-74DOI: (10.1016/j.fertnstert.2005.01.113) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions