{"paper_id":"3214dcd1-cc4c-4820-9756-cd1443c2d986","body_text":"Abstract\nObjective: To determine the effect of the 3 well-known endometriosis treatments on stem cell recruitment to endometriotic lesions. Study Design: C57BL/6 mice (aged 8 weeks, n = 20) underwent bone marrow transplant following submyeloablation with 5-fluorouracil using 20 × 106 bone marrow stem cells from green fluorescent protein (GFP) mice. Two weeks after transplantation, experimental endometriosis was created in mice by suturing segments of the uterine horn into the peritoneal cavity. Mice were then randomized to receive treatment with medroxyprogesterone acetate (MPA), leuprolide acetate (Gonadotrophin-Releasing Hormone Analogue [GnRHa]), letrozole, or vehicle control (dimethyl sulfoxide). After 3 weeks of treatment, the mice were killed and the endometriosis lesions evaluated. Results: All 3 treatments resulted in a significant reduction in lesion volume and weight. Estrogen deprivation using GnRHa or letrozole resulted in greater lesion regression than the progestin MPA. The GFP+/CD45− bone marrow-derived stem cells (BMDSCs) engrafted the lesions of endometriosis. Estrogen deprivation using GnRHa or letrozole significantly reduced BMDSC engraftment in the endometriosis lesions. MPA failed to significantly reduce stem cell number in endometriosis. Conclusion: The superiority of estrogen deprivation over progestin therapy in depriving the lesions of stem cells may have implications for the long-term treatment of endometriosis. Reduced stem cell engraftment is likely to result in long-term regression of the lesions, whereas progestins may only prevent their growth acutely.\nSimilar content being viewed by others\nReferences\nGiudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447):1789–1799.\nde Ziegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and management. Lancet. 2010;376(9742):730–738.\nMacer ML, Taylor HS. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin North Am. 2012;39(4):535–549.\nTaylor HS, Osteen KG, Bruner-Tran KL, et al. Novel therapies targeting endometriosis. Reprod Sci. 2011;18(9):814–823.\nSampson JA. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol. 1927;14(4):422–469.\nTaylor HS. Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA. 2004;292(1):81–85.\nDu H, Taylor HS. Contribution of bone marrow-derived stem cells to endometrium and endometriosis. Stem Cells. 2007;25(8):2082–2086.\nSakr S, Naqvi H, Komm B, Taylor HS. Endometriosis impairs bone marrow-derived stem cell recruitment to the uterus whereas bazedoxifene treatment leads to endometriosis regression and improved uterine stem cell engraftment. Endocrinology. 2014;155(4):1489–1497.\nTal R, Liu Y, Pluchino N, Shaikh S, Mamillapalli R, Taylor H. A murine 5-fluorouracil-based submyeloablation model for the study of bone marrow-derived cell trafficking in reproduction. Endocrinology. 2016;157(10):3749–3759.\nLee B, Du H, Taylor HS. Experimental murine endometriosis induces DNA methylation and altered gene expression in eutopic endometrium. Biol Reprod. 2009;80(1):79–85.\nFang Z, Yang S, Gurates B, et al. Genetic or enzymatic disruption of aromatase inhibits the growth of ectopic uterine tissue. J Clin Endocrinol Metab. 2002;87(7):3460–3466.\nBilotas M, Meresman G, Stella I, Sueldo C, Barañao RI. Effect of aromatase inhibitors on ectopic endometrial growth and peritoneal environment in a mouse model of endometriosis. Fertil Steril. 2010;93(8):2513–2518.\nBrodie A, Jelovac D, Long BJ. Predictions from a preclinical model: studies of aromatase inhibitors and antiestrogens. Clin Cancer Res. 2003;9(I pt 2):455–459.\nOlive DL, Pritts EA. Treatment of endometriosis. N Engl J Med. 2001;345(4):266–275.\nStrowitzki T, Marr J, Gerlinger C, Faustmann T, Seitz C. Detailed analysis of a randomized, multicenter, comparative trial of dieno-gest versus leuprolide acetate in endometriosis. Int J Gynaecol Obstet. 2012;117(3):228–233.\nRegidor PA, Regidor M, Schmidt M, et al. Prospective randomized study comparing the GnRH-agonist leuprorelin acetate and the gestagen lynestrenol in the treatment of severe endometriosis. Gynecol Endocrinol. 2001;15(3):202–209.\nThe Gestrinone Italian Study Group. Gestrinone versus a gonadotropin-releasing hormone agonist for the treatment of pelvic pain associated with endometriosis: a multicenter, randomized, double-blind study. Fertil Steril. 1996;66(6):911–919.\nGuzick DS, Huang LS, Broadman BA, Nealon M, Hornstein MD. Randomized trial of leuprolide versus continuous oral contraceptives in the treatment of endometriosis-associated pelvic pain. Fertil Steril. 2011;95(5):1568–1573.\nKulak J Jr, Fischer C, Komm B, Taylor HS. Treatment with bazedoxifene, a selective estrogen receptor modulator, causes regression of endometriosis in a mouse model. Endocrinology. 2011;152(8):3226–3232.\nWang X, Mamillapalli R, Mutlu L, Du H, Taylor HS. Chemoat-traction of bone marrow-derived stem cells towards human endometrial stromal cells is mediated by estradiol regulated CXCL12 and CXCR4 expression. Stem Cell Res. 2015;15(1):14–22.\nMoridi I, Mamillapalli R, Cosar E, Sahin Ersoy G, Taylor HS. Bone marrow stem cell chemotactic activity is induced by elevated CXCl12 in endometriosis. Reprod Sci. 2017;24(4):526–533.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nRights and permissions\nAbout this article\nCite this article\nSahin Ersoy, G., Zolbin, M.M., Cosar, E. et al. Medical Therapies for Endometriosis Differentially Inhibit Stem Cell Recruitment. Reprod. Sci. 24, 818–823 (2017). https://doi.org/10.1177/1933719116682879\nPublished:\nIssue date:\nDOI: https://doi.org/10.1177/1933719116682879","source_license":"CC0","license_restricted":false}