Effects of hormonal treatment on nerve fibers in endometrium and myometrium in women with endometriosis  Natsuko Tokushige, Ph.D., Robert Markham, Ph.D.,

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Effects of hormonal treatment on nerve fibers in endometrium and myometrium in women with endometriosis  Natsuko Tokushige, Ph.D., Robert Markham, Ph.D., Peter Russell, M.D., Ian S. Fraser, M.D.  Fertility and Sterility  Volume 90, Issue 5, Pages 1589-1598 (November 2008) DOI: 10.1016/j.fertnstert.2007.08.074 Copyright © 2008 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Nerve fibers in the functional layer and basal layer of endometrium from women with endometriosis who were receiving hormonal treatment. (A) The functional layer of endometrium from a patient with hormonally treated endometriosis, stained with PGP9.5. No nerve fibers were stained. (B) The functional layer of endometrium from a hormonally treated patient with endometriosis, stained with PGP9.5. Arrows denote several small nerve fibers in the functional layer of endometrium. (C) The basal layer of endometrium from a hormonally treated patient with endometriosis, stained with PGP9.5. Arrows denote nerve fibers in the basal layer. Fertility and Sterility 2008 90, 1589-1598DOI: (10.1016/j.fertnstert.2007.08.074) Copyright © 2008 American Society for Reproductive Medicine Terms and Conditions

Figure 2 Nerve fibers in the functional layer and basal layer of endometrium and myometrium from women with endometriosis who were receiving hormonal treatment. (A) The functional layer of endometrium from a woman with hormonally treated (progestogens) endometriosis stained with VIP. Arrows denote nerve fibers stained with VIP in the functional layer. (B) The functional layer of endometrium from a woman with hormonally treated (progestogens) endometriosis stained with NPY. Arrow denotes nerve fibers stained with NPY in the functional layer. (C) The basal layer of endometrium from a woman with hormonally treated (GnRH analogue) endometriosis stained with SP. Arrow denotes nerve fibers stained with SP in the basal layer. (D) The basal layer of endometrium from a woman with hormonally treated (progestogens) endometriosis stained with CGRP. Arrows denote nerve fibers stained with CGRP in the basal layer. (E) The basal layer of endometrium from a woman with hormonally treated (progestogens) endometriosis stained with VIP. Arrow denotes nerve fibers stained with VIP in the basal layer. (F) The basal layer of endometrium from a woman with hormonally treated (progestogens) endometriosis stained with NPY. Arrow denotes nerve fibers in the basal layer. (G) Myometrium from a woman with hormonally treated (progestogens) endometriosis stained with TH. Arrows denote nerve fibers in myometrium. (H) Myometrium from a woman with hormonally treated (progestogens) endometriosis stained with VAChT. Arrow denotes nerve fibers in myometrium. Fertility and Sterility 2008 90, 1589-1598DOI: (10.1016/j.fertnstert.2007.08.074) Copyright © 2008 American Society for Reproductive Medicine Terms and Conditions

Figure 2 Nerve fibers in the functional layer and basal layer of endometrium and myometrium from women with endometriosis who were receiving hormonal treatment. (A) The functional layer of endometrium from a woman with hormonally treated (progestogens) endometriosis stained with VIP. Arrows denote nerve fibers stained with VIP in the functional layer. (B) The functional layer of endometrium from a woman with hormonally treated (progestogens) endometriosis stained with NPY. Arrow denotes nerve fibers stained with NPY in the functional layer. (C) The basal layer of endometrium from a woman with hormonally treated (GnRH analogue) endometriosis stained with SP. Arrow denotes nerve fibers stained with SP in the basal layer. (D) The basal layer of endometrium from a woman with hormonally treated (progestogens) endometriosis stained with CGRP. Arrows denote nerve fibers stained with CGRP in the basal layer. (E) The basal layer of endometrium from a woman with hormonally treated (progestogens) endometriosis stained with VIP. Arrow denotes nerve fibers stained with VIP in the basal layer. (F) The basal layer of endometrium from a woman with hormonally treated (progestogens) endometriosis stained with NPY. Arrow denotes nerve fibers in the basal layer. (G) Myometrium from a woman with hormonally treated (progestogens) endometriosis stained with TH. Arrows denote nerve fibers in myometrium. (H) Myometrium from a woman with hormonally treated (progestogens) endometriosis stained with VAChT. Arrow denotes nerve fibers in myometrium. Fertility and Sterility 2008 90, 1589-1598DOI: (10.1016/j.fertnstert.2007.08.074) Copyright © 2008 American Society for Reproductive Medicine Terms and Conditions

Figure 3 Expression of NGF and NGFRp75 in endometrium from a woman with endometriosis who was receiving hormonal treatment and a woman with endometriosis who was not receiving hormonal treatment. (A) Endometrium from a woman with untreated endometriosis stained with NGF. (B) Endometrium from a woman with untreated endometriosis stained with NGFRp75. (C) Endometrium from a woman with hormonally treated (progestogens) endometriosis stained with NGF. (D) Endometrium from a woman with hormonally treated (progestogens) endometriosis stained with NGFRp75. Fertility and Sterility 2008 90, 1589-1598DOI: (10.1016/j.fertnstert.2007.08.074) Copyright © 2008 American Society for Reproductive Medicine Terms and Conditions