Mifepristone alters expression of endometrial steroid receptors and their cofactors in new users of medroxyprogesterone acetate  John K. Jain, M.D., Aimin Li, M.D., Wangrong Yang, M.Sc., Parviz Minoo, Ph.D., Juan C. Felix, M.D.  Fertility and Sterility  Volume 87, Issue 1, Pages 8-23 (January 2007) DOI: 10.1016/j.fertnstert.2006.05.076 Copyright © 2007 American Society for Reproductive Medicine Terms and Conditions

FIGURE 1 Immunohistochemical staining for ERα (A–H) and ERβ (I–P) in endometrium of women in the placebo group (A–D and I–L) and women in the mifepristone group (E–H and M–P). (A) Pretreatment endometrium of a woman at postovulation day 3. Note a strong glandular and mild stromal immunostaining pattern of ERα. (B) After 14 days of DMPA injection. Note a dramatic decrease of immunoreactivity in the glandular compartment. (C) After 1 week of placebo. (D) After 10 weeks of placebo. (E) Pretreatment endometrium of a woman at postovulation day 2. (F) After 14 days of DMPA injection. (G) After 1 week of mifepristone. Note a dramatic increase of glandular and stromal immunoreactivity. (H) After 10 weeks of mifepristone. Note the decrease of immunoreactivity in the glandular and stromal compartments. (I) Pretreatment endometrium of a woman at postovulation day 4. Note a mild or moderate glandular and stromal immunostaining of ERβ. (J) After 14 days of DMPA injection. (K) After 1 week of placebo. (L) After 10 weeks of placebo. (M) Pretreatment endometrium of a woman at postovulation day 5. (N) After 14 days of DMPA injection. (O) After 1 week of mifepristone. (P) After 10 weeks of mifepristone. All micrographs were photographed at ×400 original magnification; 1st, 2nd, 3rd, and 4th denote the number of biopsies that were performed. Jain. Mifepristone alters steroid receptors. Fertil Steril 2007. Fertility and Sterility 2007 87, 8-23DOI: (10.1016/j.fertnstert.2006.05.076) Copyright © 2007 American Society for Reproductive Medicine Terms and Conditions

FIGURE 2 Immunohistochemical staining for PRAB (A–H) and PRB (I–P) in endometrium of women in the placebo group (A–D and I–L) and women in the mifepristone group (E–H and M–P). (A) Pretreatment endometrium of a woman at postovulation day 3. Note a strong-to-mild glandular and stromal immunostaining pattern of PRAB. (B) After 14 days of DMPA injection. Note a dramatic decrease of immunoreactivity in the glandular compartment. (C) After 1 week of placebo. (D) After 10 weeks of placebo. (E) Pretreatment endometrium of a woman at postovulation day 2. (F) After 14 days of DMPA injection. (G) After 1 week of mifepristone. Note a dramatic increase of glandular immunoreactivity. (H) After 10 weeks of mifepristone. Note a dramatic decrease of immunoreactivity in glandular compartment. (I) Pretreatment endometrium of a woman at postovulation day 3. Note a strong-to-mild glandular and stromal immunostaining pattern of PRB. (J) After 14 days of DMPA injection. Note a dramatic decrease of immunoreactivity in the glandular compartment. (K) After 1 week of placebo. (L) After 10 weeks of placebo. (M) Pretreatment endometrium of a woman at postovulation day 2. (N) After 14 days of DMPA injection. (O) After 1 week of mifepristone. Note a dramatic increase of glandular and stromal immunoreactivity. (P) After 10 weeks of mifepristone. Note a decrease of immunoreactivity in the glandular and stromal compartments. All micrographs were photographed at ×400 original magnification; 1st, 2nd, 3rd, and 4th denote the number of biopsies that were performed. Jain. Mifepristone alters steroid receptors. Fertil Steril 2007. Fertility and Sterility 2007 87, 8-23DOI: (10.1016/j.fertnstert.2006.05.076) Copyright © 2007 American Society for Reproductive Medicine Terms and Conditions

FIGURE 3 Immunohistochemical staining for AR in endometrial glands and stroma of a woman in the placebo group (A–D) and a woman in the mifepristone group (E–H). (A and E) Pretreatment endometrium shows AR immunostaining pattern with a moderate immunoreactivity in stroma and absent or minimal immunoreactivity in glands. (B and F) After 14 days of DMPA injection. (C and G) After 1 week of placebo or mifepristone, respectively. (D and H) After 10 weeks of placebo or mifepristone, respectively. All micrographs were photographed at ×400 original magnification; 1st, 2nd, 3rd, and 4th denote the number of biopsies that were performed. Jain. Mifepristone alters steroid receptors. Fertil Steril 2007. Fertility and Sterility 2007 87, 8-23DOI: (10.1016/j.fertnstert.2006.05.076) Copyright © 2007 American Society for Reproductive Medicine Terms and Conditions

FIGURE 4 Representative photomicrographs of ERα-, PRAB-, PRB-, SRC-1–, SMRT-, and Ki-67–labeled endometrium of a woman in the placebo group. All micrographs were photographed at ×400 original magnification; 1st, 2nd, 3rd, and 4th denote the number of biopsies that were performed. Jain. Mifepristone alters steroid receptors. Fertil Steril 2007. Fertility and Sterility 2007 87, 8-23DOI: (10.1016/j.fertnstert.2006.05.076) Copyright © 2007 American Society for Reproductive Medicine Terms and Conditions

FIGURE 5 Representative photomicrographs of ERα-, PRAB-, PRB-, SRC-1–, SMRT-, and Ki-67–labeled endometrium of a woman in the mifepristone group. All micrographs were photographed at ×400 original magnification; 1st, 2nd, 3rd, and 4th denote the number of biopsies that were performed. Jain. Mifepristone alters steroid receptors. Fertil Steril 2007. Fertility and Sterility 2007 87, 8-23DOI: (10.1016/j.fertnstert.2006.05.076) Copyright © 2007 American Society for Reproductive Medicine Terms and Conditions