Endometriosis and nuclear receptors

Human Reproduction Update - Tập 25 Số 4 - Trang 473-485 - 2019
Bahar D. Yilmaz1, Serdar E. Bulun1
1Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, 250 E. Superior Street, Chicago, IL, USA

Tóm tắt

Abstract BACKGROUND Endometriosis is recognized as a steroid-dependent disorder; however, the precise roles of nuclear receptors (NRs) in steroid responsiveness and other signaling pathways are not well understood. OBJECTIVE AND RATIONALE Over the past several years, a number of paradigm-shifting breakthroughs have occurred in the area of NRs in endometriosis. We review and clarify new information regarding the mechanisms responsible for: (i) excessive estrogen biosynthesis, (ii) estrogen-dependent inflammation, (iii) defective differentiation due to progesterone resistance and (iv) enhanced survival due to deficient retinoid production and action in endometriosis. We emphasize the roles of the relevant NRs critical for these pathological processes in endometriosis. SEARCH METHODS We conducted a comprehensive search using PubMed for human, animal and cellular studies published until 2018 in the following areas: endometriosis; the steroid and orphan NRs, estrogen receptors alpha (ESR1) and beta (ESR2), progesterone receptor (PGR), steroidogenic factor-1 (NR5A1) and chicken ovalbumin upstream promoter-transcription factor II (NR2F2); and retinoids. OUTCOMES Four distinct abnormalities in the intracavitary endometrium and extra-uterine endometriotic tissue underlie endometriosis progression: dysregulated differentiation of endometrial mesenchymal cells, abnormal epigenetic marks, inflammation activated by excess estrogen and the development of progesterone resistance. Endometriotic stromal cells compose the bulk of the lesions and demonstrate widespread epigenetic abnormalities. Endometriotic stromal cells also display a wide range of abnormal NR expression. The orphan NRs NR5A1 and NR2F2 compete to regulate steroid-synthesizing genes in endometriotic stromal cells; NR5A1 dominance gives rise to excessive estrogen formation. Endometriotic stromal cells show an abnormally low ESR1:ESR2 ratio due to excessive levels of ESR2, which mediates an estrogen-driven inflammatory process and prostaglandin formation. These cells are also deficient in PGR, leading to progesterone resistance and defective retinoid synthesis. The pattern of NR expression, involving low ESR1 and PGR and high ESR2, is reminiscent of uterine leiomyoma stem cells. This led us to speculate that endometriotic stromal cells may display stem cell characteristics found in other uterine tissues. The biologic consequences of these abnormalities in endometriotic tissue include intense inflammation, defective differentiation and enhanced survival. WIDER IMPLICATIONS Steroid- and other NR-related abnormalities exert genome-wide biologic effects via interaction with defective epigenetic programming and enhance inflammation in endometriotic stromal cells. New synthetic ligands, targeting PGR, retinoic acid receptors and ESR2, may offer novel treatment options.

Từ khóa


Tài liệu tham khảo

Afshar, 2013, Changes in eutopic endometrial gene expression during the progression of experimental endometriosis in the baboon, Papio anubis, Biol Reprod, 88, 44, 10.1095/biolreprod.112.104497

Alexander, 1989, Progestin inhibition of progesterone receptor gene expression in human breast cancer cells, Mol Endocrinol, 3, 1377, 10.1210/mend-3-9-1377

Altintas, 2010, Comparison of the effects of raloxifene and anastrozole on experimental endometriosis, Eur J Obstet Gynecol Reprod Biol, 150, 84, 10.1016/j.ejogrb.2010.02.004

Altucci, 2001, Retinoic acid-induced apoptosis in leukemia cells is mediated by paracrine action of tumor-selective death ligand TRAIL, Nat Med, 7, 680, 10.1038/89050

Anglesio, 2017, Cancer-associated mutations in endometriosis without cancer, N Engl J Med, 376, 1835, 10.1056/NEJMoa1614814

Attar, 2009, Prostaglandin E2 via steroidogenic factor-1 coordinately regulates transcription of steroidogenic genes necessary for estrogen synthesis in endometriosis, J Clin Endocrinol Metab, 94, 623, 10.1210/jc.2008-1180

Attia, 2000, Progesterone receptor isoform A but not B is expressed in endometriosis, J Clin Endocrinol Metab, 85, 2897

Barragan, 2016, Human endometrial fibroblasts derived from mesenchymal progenitors inherit progesterone resistance and acquire an inflammatory phenotype in the endometrial niche in endometriosis, Biol Reprod, 94, 118, 10.1095/biolreprod.115.136010

Bartel, 2009, MicroRNAs: target recognition and regulatory functions, Cell, 136, 215, 10.1016/j.cell.2009.01.002

Bedaiwy, 2017, New developments in the medical treatment of endometriosis, Fertil Steril, 107, 555, 10.1016/j.fertnstert.2016.12.025

Bernardi, 2019, The essential role of GATA6 in the activation of estrogen synthesis in endometriosis, Reprod Sci, 26, 60, 10.1177/1933719118756751

Brandenberger, 1999, Oestrogen receptor (ER)-alpha and ER-beta isoforms in normal endometrial and endometriosis-derived stromal cells, Mol Hum Reprod, 5, 651, 10.1093/molehr/5.7.651

Bulun, 2009, Endometriosis, N Engl J Med, 360, 268, 10.1056/NEJMra0804690

Bulun, 2013, Uterine fibroids, N Engl J Med, 369, 1344, 10.1056/NEJMra1209993

Bulun, 2010, Estrogen receptor-beta, estrogen receptor-alpha, and progesterone resistance in endometriosis, Semin Reprod Med, 28, 36, 10.1055/s-0029-1242991

Bulun, 2006, Progesterone resistance in endometriosis: link to failure to metabolize estradiol, Mol Cell Endocrinol, 248, 94, 10.1016/j.mce.2005.11.041

Bulun, 2005, Regulation of aromatase expression in estrogen-responsive breast and uterine disease: from bench to treatment, Pharmacol Rev, 57, 359, 10.1124/pr.57.3.6

Bulun, 2012, Role of estrogen receptor-beta in endometriosis, Semin Reprod Med, 30, 39, 10.1055/s-0031-1299596

Burney, 2007, Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis, Endocrinology, 148, 3814, 10.1210/en.2006-1692

Çakıroğlu, 2017, Retinoid metabolism in endometriosis, J Endometr Pelvic Pain Disord, 9, 232, 10.5301/jeppd.5000309

Carroll, 2005, Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1, Cell, 122, 33, 10.1016/j.cell.2005.05.008

Casey, 1994, 17 beta-Hydroxysteroid dehydrogenase type 2: chromosomal assignment and progestin regulation of gene expression in human endometrium, J Clin Invest, 94, 2135, 10.1172/JCI117569

Caterina, 2000, Impaired nociception and pain sensation in mice lacking the capsaicin receptor, Science, 288, 306, 10.1126/science.288.5464.306

Cervello, 2010, Human endometrial side population cells exhibit genotypic, phenotypic and functional features of somatic stem cells, PLoS One, 5, e10964, 10.1371/journal.pone.0010964

Cervello, 2012, Bone marrow-derived cells from male donors do not contribute to the endometrial side population of the recipient, PLoS One, 7, e30260, 10.1371/journal.pone.0030260

Cervello, 2011, Reconstruction of endometrium from human endometrial side population cell lines, PLoS One, 6, e21221, 10.1371/journal.pone.0021221

Chabbert-Buffet, 2005, Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications, Hum Reprod Update, 11, 293, 10.1093/humupd/dmi002

Challen, 2006, A side order of stem cells: the SP phenotype, Stem Cells, 24, 3, 10.1634/stemcells.2005-0116

Chan, 2017, Co-culture with macrophages enhances the clonogenic and invasion activity of endometriotic stromal cells, Cell Prolif, 50, 10.1111/cpr.12330

Chan, 2011, Identification of cells with colony-forming activity, self-renewal capacity, and multipotency in ovarian endometriosis, Am J Pathol, 178, 2832, 10.1016/j.ajpath.2011.02.025

Chan, 2004, Clonogenicity of human endometrial epithelial and stromal cells, Biol Reprod, 70, 1738, 10.1095/biolreprod.103.024109

Cheng, 2008, Retinoic acid (RA) regulates 17beta-hydroxysteroid dehydrogenase type 2 expression in endometrium: interaction of RA receptors with specificity protein (SP) 1/SP3 for estradiol metabolism, J Clin Endocrinol Metab, 93, 1915, 10.1210/jc.2007-1536

Cho, 2018, Bufalin suppresses endometriosis progression by inducing pyroptosis and apoptosis, J Endocrinol, 237, 255, 10.1530/JOE-17-0700

Cousins, 2018, Endometrial stem/progenitor cells and their role in the pathogenesis of endometriosis, Best Pract Res Clin Obstet Gynaecol, 50, 27, 10.1016/j.bpobgyn.2018.01.011

Critchley, 2001, Estrogen receptor beta, but not estrogen receptor alpha, is present in the vascular endothelium of the human and nonhuman primate endometrium, J Clin Endocrinol Metab, 86, 1370

De Carvalho, 2007, Genetic polymorphisms of cytochrome P450cl7alpha (CYP17) and progesterone receptor genes (PROGINS) in the assessment of endometriosis risk, Gynecol Endocrinol, 23, 29, 10.1080/09513590601024707

Donaghue, 1999, Selective promoter usage of the human estrogen receptor-alpha gene and its regulation by estrogen, Mol Endocrinol, 13, 1934

Donato, 2005, Suppression of mammary carcinoma growth by retinoic acid: proapoptotic genes are targets for retinoic acid receptor and cellular retinoic acid-binding protein II signaling, Cancer Res, 65, 8193, 10.1158/0008-5472.CAN-05-1177

Donnez, 2015, Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids, Fertil Steril, 103, 519, 10.1016/j.fertnstert.2014.10.038

Du, 2012, Ischemia/reperfusion injury promotes and granulocyte-colony stimulating factor inhibits migration of bone marrow-derived stem cells to endometrium, Stem Cells Dev, 21, 3324, 10.1089/scd.2011.0193

Du, 2007, Contribution of bone marrow-derived stem cells to endometrium and endometriosis, Stem Cells, 25, 2082, 10.1634/stemcells.2006-0828

Dunselman, 2014, ESHRE guideline: management of women with endometriosis, Hum Reprod, 29, 400, 10.1093/humrep/det457

Dyson, 2015, Aberrant expression and localization of deoxyribonucleic acid methyltransferase 3B in endometriotic stromal cells, Fertil Steril, 104, 953, 10.1016/j.fertnstert.2015.06.046

Dyson, 2014, Genome-wide DNA methylation analysis predicts an epigenetic switch for GATA factor expression in endometriosis, PLoS Genet, 10, e1004158, 10.1371/journal.pgen.1004158

Fang, 2002, Genetic or enzymatic disruption of aromatase inhibits the growth of ectopic uterine tissue, J Clin Endocrinol Metab, 87, 3460, 10.1210/jcem.87.7.8683

Filigheddu, 2010, Differential expression of microRNAs between eutopic and ectopic endometrium in ovarian endometriosis, J Biomed Biotechnol, 2010, 369549, 10.1155/2010/369549

Fu, 2017, Progesterone receptor modulators for endometriosis, Cochrane Database Syst Rev, 7, Cd009881

Fujimoto, 1999, Expression of oestrogen receptor-alpha and -beta in ovarian endometriomata, Mol Hum Reprod, 5, 742, 10.1093/molehr/5.8.742

Gargett, 2010, Adult stem cells in the endometrium, Mol Hum Reprod, 16, 818, 10.1093/molehr/gaq061

Gargett, 2016, Endometrial stem/progenitor cells: the first 10 years, Hum Reprod Update, 22, 137

Germain, 2006, Overview of nomenclature of nuclear receptors, Pharmacol Rev, 58, 685, 10.1124/pr.58.4.2

Giudice, 2004, Endometriosis, Lancet, 364, 1789, 10.1016/S0140-6736(04)17403-5

Grandien, 1996, Determination of transcription start sites in the human estrogen receptor gene and identification of a novel, tissue-specific, estrogen receptor-mRNA isoform, Mol Cell Endocrinol, 116, 207, 10.1016/0303-7207(95)03716-0

Greaves, 2014, Elevated peritoneal expression and estrogen regulation of nociceptive ion channels in endometriosis, J Clin Endocrinol Metab, 99, E1738, 10.1210/jc.2014-2282

Greaves, 2015, Estradiol is a critical mediator of macrophage-nerve cross talk in peritoneal endometriosis, Am J Pathol, 185, 2286, 10.1016/j.ajpath.2015.04.012

Guo, 2014, Associations between estrogen receptor-beta polymorphisms and endometriosis risk: a meta-analysis, Diagn Pathol, 9, 184, 10.1186/s13000-014-0184-x

Halme, 1984, Retrograde menstruation in healthy women and in patients with endometriosis, Obstet Gynecol, 64, 151

Han, 2012, A new isoform of steroid receptor coactivator-1 is crucial for pathogenic progression of endometriosis, Nat Med, 18, 1102, 10.1038/nm.2826

Han, 2015, Estrogen receptor beta modulates apoptosis complexes and the inflammasome to drive the pathogenesis of endometriosis, Cell, 163, 960, 10.1016/j.cell.2015.10.034

Hanley, 2000, Steroidogenic factor 1 (SF-1) is essential for ovarian development and function, Mol Cell Endocrinol, 163, 27, 10.1016/S0303-7207(99)00237-3

Hsiao, 2015, Coordination of AUF1 and miR-148a destabilizes DNA methyltransferase 1 mRNA under hypoxia in endometriosis, Mol Hum Reprod, 21, 894, 10.1093/molehr/gav054

Hughes, 2007, Ovulation suppression for endometriosis, Cochrane Database Syst Rev, Cd000155

Huhtinen, 2012, Estrogen biosynthesis and signaling in endometriosis, Mol Cell Endocrinol, 358, 146, 10.1016/j.mce.2011.08.022

Huniadi, 2013, The effects of ulipristal on Bax/Bcl-2, cytochrome c, Ki-67 and cyclooxygenase-2 expression in a rat model with surgically induced endometriosis, Eur J Obstet Gynecol Reprod Biol, 169, 360, 10.1016/j.ejogrb.2013.03.022

Ikhena, 2018, RANKL/RANK pathway and its inhibitor RANK-Fc in uterine leiomyoma growth, J Clin Endocrinol Metab, 103, 1842, 10.1210/jc.2017-01585

Ikoma, 2009, Bone marrow-derived cells from male donors can compose endometrial glands in female transplant recipients, Am J Obstet Gynecol, 201, 608.e601, 10.1016/j.ajog.2009.07.026

Issa, 1994, Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon, Nat Genet, 7, 536, 10.1038/ng0894-536

Jabbour, 2006, Endocrine regulation of menstruation, Endocr Rev, 27, 17, 10.1210/er.2004-0021

Johnson, 2013, Consensus on current management of endometriosis, Hum Reprod, 28, 1552, 10.1093/humrep/det050

Joshi, 2017, Progesterone resistance in endometriosis is modulated by the altered expression of MicroRNA-29c and FKBP4, J Clin Endocrinol Metab, 102, 141

Kao, 2003, Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility, Endocrinology, 144, 2870, 10.1210/en.2003-0043

Kastner, 1990, Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B, EMBO J, 9, 1603, 10.1002/j.1460-2075.1990.tb08280.x

Kettel, 1996, Treatment of endometriosis with the antiprogesterone mifepristone (RU486), Fertil Steril, 65, 23, 10.1016/S0015-0282(16)58022-4

Khan, 2014, Occult microscopic endometriosis: undetectable by laparoscopy in normal peritoneum, Hum Reprod, 29, 462, 10.1093/humrep/det438

Kim, 2013, Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer, Endocr Rev, 34, 130, 10.1210/er.2012-1043

Kitareewan, 2002, UBE1L is a retinoid target that triggers PML/RARalpha degradation and apoptosis in acute promyelocytic leukemia, Proc Natl Acad Sci USA, 99, 3806, 10.1073/pnas.052011299

Kokcu, 2016, A current view of the role of epigenetic changes in the aetiopathogenesis of endometriosis, J Obstet Gynaecol, 36, 153, 10.3109/01443615.2015.1036403

Koukoura, 2016, DNA methylation in endometriosis (Review), Mol Med Rep, 13, 2939, 10.3892/mmr.2016.4925

Kulak, 2011, Treatment with bazedoxifene, a selective estrogen receptor modulator, causes regression of endometriosis in a mouse model, Endocrinology, 152, 3226, 10.1210/en.2010-1010

Kurihara, 2007, COUP-TFII mediates progesterone regulation of uterine implantation by controlling ER activity, PLoS Genet, 3, e102, 10.1371/journal.pgen.0030102

Kurita, 2000, Paracrine regulation of epithelial progesterone receptor and lactoferrin by progesterone in the mouse uterus, Biol Reprod, 62, 831, 10.1095/biolreprod62.4.831

Lattuada, 2004, Genetics of endometriosis: a role for the progesterone receptor gene polymorphism PROGINS?, Clin Endocrinol (Oxf), 61, 190, 10.1111/j.1365-2265.2004.02076.x

Lessey, 1983, The subunit structure of human breast cancer progesterone receptors: characterization by chromatography and photoaffinity labeling, Endocrinology, 112, 1267, 10.1210/endo-112-4-1267

Li, 2014, Isolation and identification of epithelial and stromal stem cells from eutopic endometrium of women with endometriosis, Eur J Obstet Gynecol Reprod Biol, 178, 89, 10.1016/j.ejogrb.2014.04.001

Li, 2013, COUP-TFII regulates human endometrial stromal genes involved in inflammation, Mol Endocrinol, 27, 2041, 10.1210/me.2013-1191

Liang, 2018, Efficacy, safety and recurrence of new progestins and selective progesterone receptor modulator for the treatment of endometriosis: a comparison study in mice, Reprod Biol Endocrinol, 16, 32, 10.1186/s12958-018-0347-9

Lin, 2014, Suppression of COUP-TFII by proinflammatory cytokines contributes to the pathogenesis of endometriosis, J Clin Endocrinol Metab, 99, E427, 10.1210/jc.2013-3717

Lin, 2007, Novel estrogen receptor-alpha binding sites and estradiol target genes identified by chromatin immunoprecipitation cloning in breast cancer, Cancer Res, 67, 5017, 10.1158/0008-5472.CAN-06-3696

Lin, 2009, Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation, Cancer Res, 69, 5415, 10.1158/0008-5472.CAN-08-1622

Lu, 2018, Retinoic acid regulates endometriotic stromal cell growth through upregulation of Beclin1, Arch Gynecol Obstet, 297, 93, 10.1007/s00404-017-4549-8

Luo, 1994, A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation, Cell, 77, 481, 10.1016/0092-8674(94)90211-9

Madauss, 2007, The evolution of progesterone receptor ligands, Med Res Rev, 27, 374, 10.1002/med.20083

Mas, 2012, Identification and characterization of the human leiomyoma side population as putative tumor-initiating cells, Fertil Steril, 98, 741, 10.1016/j.fertnstert.2012.04.044

Masuda, 2012, A novel marker of human endometrial mesenchymal stem-like cells, Cell Transplant, 21, 2201, 10.3727/096368911X637362

Masuda, 2010, Stem cell-like properties of the endometrial side population: implication in endometrial regeneration, PLoS One, 5, e10387, 10.1371/journal.pone.0010387

Matsuzaki, 2001, Expression of estrogen receptor alpha and beta in peritoneal and ovarian endometriosis, Fertil Steril, 75, 1198, 10.1016/S0015-0282(01)01783-6

Mei, 2010, A novel mifepristone-loaded implant for long-term treatment of endometriosis: in vitro and in vivo studies, Eur J Pharm Sci, 39, 421, 10.1016/j.ejps.2010.01.012

Milingos, 2003, Laparoscopic management of patients with endometriosis and chronic pelvic pain, Ann N Y Acad Sci, 997, 269, 10.1196/annals.1290.030

Miyazaki, 2012, Stem cell-like differentiation potentials of endometrial side population cells as revealed by a newly developed in vivo endometrial stem cell assay, PLoS One, 7, e50749, 10.1371/journal.pone.0050749

Monsivais, 2014, ERbeta- and prostaglandin E2-regulated pathways integrate cell proliferation via Ras-like and estrogen-regulated growth inhibitor in endometriosis, Mol Endocrinol, 28, 1304, 10.1210/me.2013-1421

Monsivais, 2016, Estrogen receptor beta regulates endometriotic cell survival through serum and glucocorticoid-regulated kinase activation, Fertil Steril, 105, 1266, 10.1016/j.fertnstert.2016.01.012

Monteiro, 2014, Endometriosis is characterized by a distinct pattern of histone 3 and histone 4 lysine modifications, Reprod Sci, 21, 305, 10.1177/1933719113497267

Montgomery, 2008, The search for genes contributing to endometriosis risk, Hum Reprod Update, 14, 447, 10.1093/humupd/dmn016

Mor-Vaknin, 2003, Vimentin is secreted by activated macrophages, Nat Cell Biol, 5, 59, 10.1038/ncb898

Mosselman, 1996, ER beta: identification and characterization of a novel human estrogen receptor, FEBS Lett, 392, 49, 10.1016/0014-5793(96)00782-X

Mote, 1999, Colocalization of progesterone receptors A and B by dual immunofluorescent histochemistry in human endometrium during the menstrual cycle, J Clin Endocrinol Metab, 84, 2963

Mulac-Jericevic, 2003, Defective mammary gland morphogenesis in mice lacking the progesterone receptor B isoform, Proc Natl Acad Sci USA, 100, 9744, 10.1073/pnas.1732707100

Mulac-Jericevic, 2000, Subgroup of reproductive functions of progesterone mediated by progesterone receptor-B isoform, Science, 289, 1751, 10.1126/science.289.5485.1751

Naqvi, 2014, Treatment with bazedoxifene and conjugated estrogens results in regression of endometriosis in a murine model, Biol Reprod, 90, 121, 10.1095/biolreprod.113.114165

Noble, 1997, Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells, J Clin Endocrinol Metab, 82, 600

Ohlsson Teague, 2009, MicroRNA-regulated pathways associated with endometriosis, Mol Endocrinol, 23, 265, 10.1210/me.2008-0387

Ong, 2018, Bone marrow stem cells do not contribute to endometrial cell lineages in chimeric mouse models, Stem Cells, 36, 91, 10.1002/stem.2706

Ono, 2012, Role of stem cells in human uterine leiomyoma growth, PLoS One, 7, e36935, 10.1371/journal.pone.0036935

Ottaviano, 1994, Methylation of the estrogen receptor gene CpG island marks loss of estrogen receptor expression in human breast cancer cells, Cancer Res, 54, 2552

Pabalan, 2014, Association of the progesterone receptor gene polymorphism (PROGINS) with endometriosis: a meta-analysis, Arch Gynecol Obstet, 290, 1015, 10.1007/s00404-014-3308-3

Pan, 2008, MicroRNA signature and regulatory functions in the endometrium during normal and disease states, Semin Reprod Med, 26, 479, 10.1055/s-0028-1096128

Pavone, 2011, Endometriosis expresses a molecular pattern consistent with decreased retinoid uptake, metabolism and action, Hum Reprod, 26, 2157, 10.1093/humrep/der172

Pavone, 2017, Altered retinoid signaling compromises decidualization in human endometriotic stromal cells, Reproduction, 154, 107, 10.1530/REP-16-0592

Pavone, 2010, Altered retinoid uptake and action contributes to cell survival in endometriosis, J Clin Endocrinol Metab, 95, E300, 10.1210/jc.2010-0459

Pei, 2018, miR-194-3p represses the progesterone receptor and decidualization in eutopic endometrium from women with endometriosis, Endocrinology, 159, 2554, 10.1210/en.2018-00374

Pierzchalski, 2014, Retinoic acid biosynthesis is impaired in human and murine endometriosis, Biol Reprod, 91, 84, 10.1095/biolreprod.114.119677

Rahmioglu, 2012, Insights into assessing the genetics of endometriosis, Curr Obstet Gynecol Rep, 1, 124, 10.1007/s13669-012-0016-5

Rizner, 2016, The important roles of steroid sulfatase and sulfotransferases in gynecological diseases, Front Pharmacol, 7, 30, 10.3389/fphar.2016.00030

Sampson, 1927, Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous Circulation, Am J Pathol, 3, 93

Santamaria, 2016, Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman’s syndrome and endometrial atrophy: a pilot cohort study, Hum Reprod, 31, 1087, 10.1093/humrep/dew042

Schug, 2007, Opposing effects of retinoic acid on cell growth result from alternate activation of two different nuclear receptors, Cell, 129, 723, 10.1016/j.cell.2007.02.050

Schwab, 2005, Putative stem cell activity of human endometrial epithelial and stromal cells during the menstrual cycle, Fertil Steril, 84, 1124, 10.1016/j.fertnstert.2005.02.056

Schwab, 2007, Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium, Hum Reprod, 22, 2903, 10.1093/humrep/dem265

Shang, 2006, Molecular mechanisms of oestrogen and SERMs in endometrial carcinogenesis, Nat Rev Cancer, 6, 360, 10.1038/nrc1879

Shaw, 2003, Retinoic acid is a high affinity selective ligand for the peroxisome proliferator-activated receptor beta/delta, J Biol Chem, 278, 41589, 10.1074/jbc.C300368200

Shen, 2013, MicroRNA23a and microRNA23b deregulation derepresses SF-1 and upregulates estrogen signaling in ovarian endometriosis, J Clin Endocrinol Metab, 98, 1575, 10.1210/jc.2012-3010

Simpson, 1980, Heritable aspects of endometriosis. I. Genetic studies, Am J Obstet Gynecol, 137, 327, 10.1016/0002-9378(80)90917-5

Sirianni, 2009, Inhibition of cyclooxygenase-2 down-regulates aromatase activity and decreases proliferation of Leydig tumor cells, J Biol Chem, 284, 28905, 10.1074/jbc.M109.041020

Smuc, 2007, Expression analysis of the genes involved in estradiol and progesterone action in human ovarian endometriosis, Gynecol Endocrinol, 23, 105, 10.1080/09513590601152219

Soysal, 2004, The effects of post-surgical administration of goserelin plus anastrozole compared to goserelin alone in patients with severe endometriosis: a prospective randomized trial, Hum Reprod, 19, 160, 10.1093/humrep/deh035

Stovall, 1997, Endometriosis-associated pelvic pain: evidence for an association between the stage of disease and a history of chronic pelvic pain, Fertil Steril, 68, 13, 10.1016/S0015-0282(97)81468-9

Stratton, 2008, Return of chronic pelvic pain from endometriosis after raloxifene treatment: a randomized controlled trial, Obstet Gynecol, 111, 88, 10.1097/01.AOG.0000297307.35024.b5

Sun, 2003, Transactivation of steroidogenic acute regulatory protein in human endometriotic stromalcells is mediated by the prostaglandin EP2 receptor, Endocrinology, 144, 3934, 10.1210/en.2003-0289

Takayama, 1998, Treatment of severe postmenopausal endometriosis with an aromatase inhibitor, Fertil Steril, 69, 709, 10.1016/S0015-0282(98)00022-3

Tamura, 2004, Estrogen up-regulates cyclooxygenase-2 via estrogen receptor in human uterine microvascular endothelial cells, Fertil Steril, 81, 1351, 10.1016/j.fertnstert.2003.09.076

Tamura, 2002, Interleukin-1beta elevates cyclooxygenase-2 protein level and enzyme activity via increasing its mRNA stability in human endometrial stromal cells: an effect mediated by extracellularly regulated kinases 1 and 2, J Clin Endocrinol Metab, 87, 3263

Tan, 2002, Selective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription, Mol Cell Biol, 22, 5114, 10.1128/MCB.22.14.5114-5127.2002

Taylor, 2004, Endometrial cells derived from donor stem cells in bone marrow transplant recipients, J Am Med Assoc, 292, 81, 10.1001/jama.292.1.81

Trukhacheva, 2009, Estrogen receptor (ER) beta regulates ERalpha expression in stromal cells derived from ovarian endometriosis, J Clin Endocrinol Metab, 94, 615, 10.1210/jc.2008-1466

Ulrich, 2014, Mesenchymal stem/stromal cells in post-menopausal endometrium, Hum Reprod, 29, 1895, 10.1093/humrep/deu159

Utsunomiya, 2008, Upstream stimulatory factor-2 regulates steroidogenic factor-1 expression in endometriosis, Mol Endocrinol, 22, 904, 10.1210/me.2006-0302

van Kaam, 2011, Deoxyribonucleic acid methyltransferases and methyl-CpG-binding domain proteins in human endometrium and endometriosis, Fertil Steril, 95, 1421, 10.1016/j.fertnstert.2011.01.031

van Kaam, 2007, Progesterone receptor polymorphism +331G/A is associated with a decreased risk of deep infiltrating endometriosis, Hum Reprod, 22, 129, 10.1093/humrep/del325

Vegeto, 1993, Human progesterone receptor A form is a cell- and promoter-specific repressor of human progesterone receptor B function, Mol Endocrinol, 7, 1244

Vercellini, 2011, Oral contraceptives and risk of endometriosis: a systematic review and meta-analysis, Hum Reprod Update, 17, 159, 10.1093/humupd/dmq042

Vercellini, 2014, Endometriosis: pathogenesis and treatment, Nat Rev Endocrinol, 10, 261, 10.1038/nrendo.2013.255

Wang, 2007, Retinoic acid enhances the production of IL-10 while reducing the synthesis of IL-12 and TNF-alpha from LPS-stimulated monocytes/macrophages, J Clin Immunol, 27, 193, 10.1007/s10875-006-9068-5

Weihua, 2000, Estrogen receptor (ER) beta, a modulator of ERalpha in the uterus, Proc Natl Acad Sci U S A, 97, 5936, 10.1073/pnas.97.11.5936

Whitaker, 2014, Selective progesterone receptor modulators, Curr Opin Obstet Gynecol, 26, 237, 10.1097/GCO.0000000000000082

Wieser, 2002, PROGINS receptor gene polymorphism is associated with endometriosis, Fertil Steril, 77, 309, 10.1016/S0015-0282(01)02984-3

Wieser, 2012, Retinoic acid suppresses growth of lesions, inhibits peritoneal cytokine secretion, and promotes macrophage differentiation in an immunocompetent mouse model of endometriosis, Fertil Steril, 97, 1430, 10.1016/j.fertnstert.2012.03.004

Wu, 2008, Prolonged stimulation with tumor necrosis factor-alpha induced partial methylation at PR-B promoter in immortalized epithelial-like endometriotic cells, Fertil Steril, 90, 234, 10.1016/j.fertnstert.2007.06.008

Wu, 2006, Promoter hypermethylation of progesterone receptor isoform B (PR-B) in endometriosis, Epigenetics, 1, 106, 10.4161/epi.1.2.2766

Wu, 2005, Distinct regulation of cyclooxygenase-2 by interleukin-1beta in normal and endometriotic stromal cells, J Clin Endocrinol Metab, 90, 286, 10.1210/jc.2004-1612

Xue, 2007, Promoter methylation regulates estrogen receptor 2 in human endometrium and endometriosis, Biol Reprod, 77, 681, 10.1095/biolreprod.107.061804

Xue, 2007, Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5’ CpG island in endometriosis, J Clin Endocrinol Metab, 92, 3261, 10.1210/jc.2007-0494

Xue, 2014, Methylation of a novel CpG island of intron 1 is associated with steroidogenic factor 1 expression in endometriotic stromal cells, Reprod Sci, 21, 395, 10.1177/1933719113497283

Xue, 2011, Hypermethylation of the CpG island spanning from exon II to intron III is associated with steroidogenic factor 1 expression in stromal cells of endometriosis, Reprod Sci, 18, 1080, 10.1177/1933719111404614

Yamagata, 2014, Genome-wide DNA methylation profiling in cultured eutopic and ectopic endometrial stromal cells, PLoS One, 9, e83612, 10.1371/journal.pone.0083612

Yang, 2001, Stromal PRs mediate induction of 17beta-hydroxysteroid dehydrogenase type 2 expression in human endometrial epithelium: a paracrine mechanism for inactivation of E2, Mol Endocrinol, 15, 2093

Yang, 2002, Regulation of aromatase P450 expression in endometriotic and endometrial stromal cells by CCAAT/enhancer binding proteins (C/EBPs): decreased C/EBPbeta in endometriosis is associated with overexpression of aromatase, J Clin Endocrinol Metab, 87, 2336

Yang, 2015, Integrative analysis reveals regulatory programs in endometriosis, Reprod Sci, 22, 1060, 10.1177/1933719115592709

Yang, 2011, Progesterone: the ultimate endometrial tumor suppressor, Trends Endocrinol Metab, 22, 145, 10.1016/j.tem.2011.01.005

Yang, 2012, FKBP4 is regulated by HOXA10 during decidualization and in endometriosis, Reproduction, 143, 531, 10.1530/REP-11-0438

Yao, 2005, Validation of rat endometriosis model by using raloxifene as a positive control for the evaluation of novel SERM compounds, J Invest Surg, 18, 177, 10.1080/08941930591004412

Yin, 2013, Expression profiling of nuclear receptors identifies key roles of NR4A subfamily in uterine fibroids, Mol Endocrinol, 27, 726, 10.1210/me.2012-1305

Yotova, 2017, Epigenetic alterations affecting transcription factors and signaling pathways in stromal cells of endometriosis, PLoS One, 12, e0170859, 10.1371/journal.pone.0170859

Zeitoun, 1999, Stimulation of aromatase P450 promoter (II) activity in endometriosis and its inhibition in endometrium are regulated by competitive binding of steroidogenic factor-1 and chicken ovalbumin upstream promoter transcription factor to the same cis-acting element, Mol Endocrinol, 13, 239, 10.1210/mend.13.2.0229

Zhao, 2015, Dual suppression of estrogenic and inflammatory activities for targeting of endometriosis, Sci Transl Med, 7, 271ra279, 10.1126/scitranslmed.3010626

Zhou, 2016, miR-196a overexpression activates the MEK/ERK signal and represses the progesterone receptor and decidualization in eutopic endometrium from women with endometriosis, Hum Reprod, 31, 2598, 10.1093/humrep/dew223

Zhou, 2001, The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype, Nat Med, 7, 1028, 10.1038/nm0901-1028