Promoter Methylation Regulates Estrogen Receptor 2 in Human Endometrium and Endometriosis1
Abstract
Steroid receptors in the stromal cells of endometrium and its disease counterpart tissue endometriosis play critical physiologic roles. We found that mRNA and protein levels of estrogen receptor 2 (ESR2) were strikingly higher, whereas levels of estrogen receptor 1 (ESR1), total progesterone receptor (PGR), and progesterone receptor B (PGR B) were significantly lower in endometriotic versus endometrial stromal cells. Because ESR2 displayed the most striking levels of differential expression between endometriotic and endometrial cells, and the mechanisms for this difference are unknown, we tested the hypothesis that alteration in DNA methylation is a mechanism responsible for severely increased ESR2 mRNA levels in endometriotic cells. We identified a CpG island occupying the promoter region (-197/+359) of the ESR2 gene. Bisulfite sequencing of this region showed significantly higher methylation in primary endometrial cells (n = 8 subjects) versus endometriotic cells (n = 8 subjects). The demethylating agent 5-aza-2'-deoxycytidine significantly increased ESR2 mRNA levels in endometrial cells. Mechanistically, we employed serial deletion mutants of the ESR2 promoter fused to the luciferase reporter gene and transiently transfected into both endometriotic and endometrial cells. We demonstrated that the critical region (-197/+372) that confers promoter activity also bears the CpG island, and the activity of the ESR2 promoter was strongly inactivated by in vitro methylation. Taken together, methylation of a CpG island at the ESR2 promoter region is a primary mechanism responsible for differential expression of ESR2 in endometriosis and endometrium. These findings may be applied to a number of areas ranging from diagnosis to the treatment of endometriosis.
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ERβ is hypermethylated and silenced in normal endometrial stromal cells.
“In addition, ERβ is also hypermethylated and silenced in normal endometrial stromal cells [71].”
From The Pathogenesis of Adenomyosis vis-à-vis Endometriosis (2020) · cites this paper as [71]
Higher expression of estrogen receptor amplifies estrogenic effects and the proliferative capacity of endometrial cells.
“Higher expression of estrogen receptor amplifies estrogenic effects and the proliferative capacity of endometrial cells.26,27”
From Altered genome-wide methylation in endometriosis (2014) · cites this paper as [27]
Cites
Cloning of a novel receptor expressed in rat prostate and ovary.
Kuiper, G. G. J. M., Enmark, E., Pelto‐Huikko, M., Nilsson, S., & Gustafsson, J.-Α. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.12.5925 · Cited by 4,792 · see citing works
Kuiper, G. G. J. M., Carlsson, B., Grandien, K., Enmark, E., Häggblad, J., Nilsson, S., & Gustafsson, J.-A. (1997) · Endocrinology · doi:10.1210/endo.138.3.4979 · Cited by 4,442 · see citing works
Giudice, L. C., & Kao, L. C. (2004) · The Lancet · doi:10.1016/s0140-6736(04)17403-5 · Cited by 3,166 · see citing works
Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription
Jones, P. L., Veenstra, G. J. C., Wade, P. A., Vermaak, D., Kass, S. U., Landsberger, N., Strouboulis, J., & Wolffe, A. P. (1998) · Nature Genetics · doi:10.1038/561 · Cited by 2,734 · see citing works
Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A
Green, S., Walter, P., Kumar, V., Krust, A., Bornert, J., Argos, P., & Chambon, P. (1986) · Nature · doi:10.1038/320134a0 · Cited by 2,320 · see citing works
ERβ: Identification and characterization of a novel human estrogen receptor
Mosselman, S., Polman, J., & Dijkema, R. (1996) · FEBS Letters · doi:10.1016/0014-5793(96)00782-x · Cited by 2,269 · see citing works
Generation and reproductive phenotypes of mice lacking estrogen receptor β
Krege, J. H., Hodgin, J. B., Couse, J. F., Enmark, E., Warner, M. N., Mahler, J. F., Sar, M., Korach, K. S., Gustafsson, J.-Α., & Smithies, O. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.26.15677 · Cited by 1,692 · see citing works
Eskenazi, B., & Warner, M. L. (1997) · Obstetrics and Gynecology Clinics of North America · doi:10.1016/s0889-8545(05)70302-8 · Cited by 1,617 · see citing works
Hall, J. M., & McDonnell, D. P. (1999) · Endocrinology · doi:10.1210/endo.140.12.7179 · Cited by 1,078 · see citing works
Estrogen Receptors α and β Form Heterodimers on DNA
Cowley, S. M., Hoare, S., Mosselman, S., & Parker, M. G. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.32.19858 · Cited by 689 · see citing works
Bulun, S. E., Lin, Z., Imir, G., Amin, S., Demura, M., Yilmaz, B., Martin, R., Utsunomiya, H., Thung, S., Gurates, B., et al. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.3.6 · Cited by 531 · see citing works
Self-citationProgesterone Receptor Isoform A But Not B Is Expressed in Endometriosis
Attia, G. R. (2000) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.8.2897 · Cited by 488 · see citing works
Progesterone resistance in endometriosis: link to failure to metabolize estradiol.
Bulun, S. E., Cheng, Y.-H., Yin, P., Imir, G., Utsunomiya, H., Attar, E., Innes, J., & Julie Kim, J. (2006) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2005.11.041 · Cited by 397 · see citing works
Self-citationProstaglandin E2 Stimulates Aromatase Expression in Endometriosis-Derived Stromal Cells
Noble, L. S. (1997) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.82.2.600 · Cited by 301 · see citing works
Self-citationEstrogen Receptor-β: Recent Lessons from in Vivo Studies
Harris, H. A. (2006) · Molecular Endocrinology · doi:10.1210/me.2005-0459 · Cited by 278 · see citing works
Epidemiology of endometriosis-associated infertility.
Wheeler, J. M. (1989) · PubMed · Cited by 270 · see citing works
Aromatase and other steroidogenic genes in endometriosis: translational aspects.
Attar, E., & Bulun, S. E. (2006) · Human Reproduction Update · doi:10.1093/humupd/dmi034 · Cited by 255 · see citing works
Self-citationIsolation, characterization, and comparison of human endometrial and endometriosis cells in vitro
Ryan, I., Schriock, E. D., & Taylor, R. N. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.78.3.8126136 · Cited by 250 · see citing works
The Ski protein family is required for MeCP2-mediated transcriptional repression.
Kokura, K., Kaul, S. C., Wadhwa, R., Nomura, T., Khan, M. M., Shinagawa, T., Yasukawa, T., Colmenares, C., & Ishii, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105747200 · Cited by 222 · see citing works
Zhu, X., Leav, I., Leung, Y., Wu, M., Liu, Q., Gao, Y. J., McNeal, J. E., & Ho, S. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63760-1 · Cited by 205 · see citing works
Zhao, C., Lam, E. W. ‐., Sunters, A., Enmark, E., Bella, M. T. D., Coombes, R. C., Gustafsson, J.-Α., & Dahlman‐Wright, K. (2003) · Oncogene · doi:10.1038/sj.onc.1207100 · Cited by 168 · see citing works
Brandenberger, A. W. (1999) · Molecular Human Reproduction · doi:10.1093/molehr/5.7.651 · Cited by 165 · see citing works
Sasaki, M., Dharia, A., Oh, B. R., Tanaka, Y., Fujimoto, S., & Dahiya, R. (2001) · PubMed · Cited by 147 · see citing works
Ferguson, A. T., Vertino, P. M., Spitzner, J. R., Baylin, S. B., Muller, M. T., & Davidson, N. E. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.51.32260 · Cited by 146 · see citing works
QSAR Models for Binding of Estrogenic Compounds to Estrogen Receptor α and β Subtypes
Tong, W., Perkins, R., Xing, L., Welsh, W. J., & Sheehan, D. M. (1997) · Endocrinology · doi:10.1210/endo.138.9.5487 · Cited by 127 · see citing works
DNA hypermethylation: when tumour suppressor genes go silent
Garinis, G. A., Patrinos, G. P., Spanakis, N. E., & Menounos, P. G. (2002) · Human Genetics · doi:10.1007/s00439-002-0783-6 · Cited by 127 · see citing works
Expression of oestrogen receptor-alpha and -beta in ovarian endometriomata
Fujimoto, J. (1999) · Molecular Human Reproduction · doi:10.1093/molehr/5.8.742 · Cited by 123 · see citing works
Harris, H. A., Bruner‐Tran, K. L., Zhang, X., Osteen, K. G., & Lyttle, C. R. (2004) · Human Reproduction · doi:10.1093/humrep/deh711 · Cited by 119 · see citing works
Steroid receptor and aromatase expression in baboon endometriotic lesions
Fazleabas, A. T., Brudney, A., Chai, D. C., Langoi, D., & Bulun, S. E. (2003) · Fertility and Sterility · doi:10.1016/s0015-0282(03)00982-8 · Cited by 111 · see citing works
Self-citationHistone deacetylases: complex transducers of nuclear signals
Johnson, C. A., & Turner, B. M. (1999) · Seminars in Cell and Developmental Biology · doi:10.1006/scdb.1999.0299 · Cited by 110 · see citing works
Song, S. H., Jong, H. S., Choi, H. H., Inoue, H., Tanabe, T., Kim, N. K., & Bang, Y. J. (2001) · PubMed · Cited by 107 · see citing works
Cloning and Characterization of Human Estrogen Receptor β Promoter
Li, L., Yeh, C., Nojima, D., & Dahiya, R. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3363 · Cited by 104 · see citing works
Singal, R., Ferris, R. C., Little, J. A., Wang, S.-Z., & Ginder, G. (1997) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.94.25.13724 · Cited by 93 · see citing works
Rody, A., Holtrich, U., Solbach, C., Kourtis, K., von Minckwitz, G., Engels, K., Kissler, S., Gätje, R., Karn, T., & Kaufmann, M. (2005) · Endocrine Related Cancer · doi:10.1677/erc.1.01088 · Cited by 81 · see citing works
Sasaki, M., Oh, B. R., Dharia, A., Fujimoto, S., & Dahiya, R. (2000) · Molecular Carcinogenesis · doi:10.1002/1098-2744(200010)29:2 · Cited by 70 · see citing works
Poelzl, G., Kasai, Y., Mochizuki, N., Shaul, P. W., Brown, M. A., & Mendelsohn, M. E. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.050580997 · Cited by 57 · see citing works
Tomikawa, J., Fukatsu, K., Tanaka, S., & Shiota, K. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m513782200 · Cited by 50 · see citing works
Robertson, K. D., & Ambinder, R. F. (1997) · Journal of Virology · doi:10.1128/jvi.71.9.6445-6454.1997 · Cited by 49 · see citing works
Epigenetic Inactivation of Betaig-h3 Gene in Human Cancer Cells
Shao, G., Berenguer, J., Borczuk, A., Powell, C. A., Hei, T. K., & Zhao, Y. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2130 · Cited by 46 · see citing works
Endometriosis, 1995 - confusion or sense?
Thomas, E. (1995) · International Journal of Gynecology & Obstetrics · doi:10.1016/0020-7292(94)02277-6 · Cited by 42 · see citing works
DNA Methylation as a Cancer‐Specific Biomarker
Patel, A. C., Groopman, J. D., & Umar, A. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb05983.x · Cited by 34 · see citing works
Preliminary report on the use of tamoxifen in the treatment of endometriosis
Haber, G., & Behelak, Y. (1987) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(87)90057-3 · Cited by 22 · see citing works
Flagged first, then by citations
1 of the 43 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Endometriosis: pathogenesis and treatment
Vercellini, P., Viganò, P., Somigliana, E., & Fedele, L. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.255 · Cited by 1,940 · see citing works
Bulun, S. E. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0804690 · Cited by 1,772 · see citing works
Self-citationEndometriosis is a chronic systemic disease: Clinical challenges and novel innovations
Taylor, H. S., Kotlyar, A. M., & Flores, V. A. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00389-5 · Cited by 1,425 · see citing works
Bulun, S. E., Yilmaz, B. D., Sison, C., Miyazaki, K., Bernardi, L., Liu, S., Kohlmeier, A., Yin, P., Milad, M., & Wei, J. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00242 · Cited by 844 · see citing works
Self-citationProgesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer
Kim, J. J., Kurita, T., & Bulun, S. E. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1043 · Cited by 520 · see citing works
Self-citationProgesterone and Estrogen Signaling in the Endometrium: What Goes Wrong in Endometriosis?
Marquardt, R. M., Kim, T. H., Shin, J., & Jeong, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20153822 · Cited by 510 · see citing works
The Pathogenesis of Endometriosis: Molecular and Cell Biology Insights
Laganà, A. S., Garzon, S., Götte, M., Viganò, P., Franchi, M. P., Ghezzi, F., & Martin, D. C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225615 · Cited by 492 · see citing works
The Origin and Pathogenesis of Endometriosis
Wang, Y., Nicholes, K., & Shih, I. (2019) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012419-032654 · Cited by 466 · see citing works
Han, S. J., Jung, S. Y., Wu, S.-P., Hawkins, S. M., Park, M. J., Kyo, S., Qin, J., Lydon, J. P., Tsai, S. Y., Tsai, M.-J., et al. (2015) · Cell · doi:10.1016/j.cell.2015.10.034 · Cited by 380 · see citing works
Hormonal treatments for endometriosis: The endocrine background
Vannuccini, S., Clemenza, S., Rossi, M., & Petraglia, F. (2022) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09666-w · Cited by 336 · see citing works
“Changes in promoter methylation may be a cause for the increased ERβ/ERα ratio in endometriotic cells, since regions of the ERα promoter become hypermethylated leading to a decreased expression, whereas a CpG island in the ERβ promoter becomes hypomethylated causing an increased expression [41, 42] (Fig.”
BackgroundProgesterone resistance in endometriosis: origins, consequences and interventions
Patel, B. G., Rudnicki, M., Yu, J., Shu, Y., & Taylor, R. N. (2017) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1111/aogs.13156 · Cited by 336 · see citing works
Guo, S.-W. (2009) · Molecular Human Reproduction · doi:10.1093/molehr/gap064 · Cited by 328 · see citing works
Estrogen Receptor β: An Overview and Update
Zhao, C., Dahlman‐Wright, K., & Gustafsson, J.-Α. (2008) · Nuclear Receptor Signaling · doi:10.1621/nrs.06003 · Cited by 311 · see citing works
Role of Estrogen Receptor-β in Endometriosis
Bulun, S., Monsavais, D., Pavone, M., Dyson, M., Xue, Q., Attar, E., Tokunaga, H., & Su, E. (2012) · Seminars in Reproductive Medicine · doi:10.1055/s-0031-1299596 · Cited by 307 · see citing works
Self-citationRole of estrogen receptors in health and disease
Chen, P., Li, B., & Ou-Yang, L. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.839005 · Cited by 339 · see citing works
Estrogen Receptors and Endometriosis
Chantalat, É., Valera, M., Vaysse, C., Noirrit‐Esclassan, E., Rusidzé, M., Weyl, A., Vergriete, K., Buscail, É., Lluel, P., Fontaine, C., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082815 · Cited by 315 · see citing works
Estrogen receptors and human disease: an update
Burns, K. A., & Korach, K. (2012) · Archives of Toxicology · doi:10.1007/s00204-012-0868-5 · Cited by 287 · see citing works
Endometriosis and nuclear receptors
Yilmaz, B. D., & Bulun, S. E. (2019) · Human Reproduction Update · doi:10.1093/humupd/dmz005 · Cited by 243 · see citing works
Self-citationEstrogen Receptor-β, Estrogen Receptor-α, and Progesterone Resistance in Endometriosis
Bulun, S., Cheng, Y.-H., Pavone, M., Xue, Q., Attar, E., Trukhacheva, E., Tokunaga, H., Utsunomiya, H., Yin, P., Luo, X., et al. (2010) · Seminars in Reproductive Medicine · doi:10.1055/s-0029-1242991 · Cited by 243 · see citing works
Self-citationEndometriosis and adenomyosis: shared pathophysiology
Bulun, S. E., Yildiz, S., Adli, M., Chakravarti, D., Parker, J. B., Milad, M., Yang, L., Chaudhari, A., Tsai, S., Wei, J. J., et al. (2023) · Fertility and Sterility · doi:10.1016/j.fertnstert.2023.03.006 · Cited by 216 · see citing works
Self-citationAdenomyosis pathogenesis: insights from next-generation sequencing
Bulun, S. E., Yıldız, Ş., Adli, M., & Wei, J. (2021) · Human Reproduction Update · doi:10.1093/humupd/dmab017 · Cited by 211 · see citing works
Self-citationRegulation of Inflammation Pathways and Inflammasome by Sex Steroid Hormones in Endometriosis
García-Gómez, E., Vázquez-Martínez, E. R., Reyes-Mayoral, C., Cruz-Orozco, O., Camacho‐Arroyo, I., & Cerbón, M. A. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00935 · Cited by 198 · see citing works
Huhtinen, K., Desai, R., Ståhle, M., Salminen, A., Handelsman, D. J., Perheentupa, A., & Poutanen, M. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1154 · Cited by 195 · see citing works
Greaves, E., Cousins, F., Murray, A., Esnal-Zufiaurre, A., Fassbender, A., Horne, A., & Saunders, P. (2014) · American Journal of Pathology · doi:10.1016/j.ajpath.2014.03.011 · Cited by 170 · see citing works
Kinase signalling pathways in endometriosis: potential targets for non-hormonal therapeutics
McKinnon, B. D., Kocbek, V., Nirgianakis, K., Bersinger, N. A., & Mueller, M. D. (2016) · Human Reproduction Update · doi:10.1093/humupd/dmv060 · Cited by 194 · see citing works
Endometrial receptivity in women of advanced age: an underrated factor in infertility
Pathare, A. D. S., Loid, M., Saare, M., Gidlöf, S. B., Esteki, M. Z., Acharya, G., Peters, M., & Salumets, A. (2023) · Human Reproduction Update · doi:10.1093/humupd/dmad019 · Cited by 185 · see citing works
Zama, A. M., & Uzumcu, M. (2009) · Endocrinology · doi:10.1210/en.2009-0499 · Cited by 174 · see citing works
Molecular and Cellular Pathogenesis of Endometriosis
Klemmt, P. A. B., & Starzinski‐Powitz, A. (2017) · Current Women s Health Reviews · doi:10.2174/1573404813666170306163448 · Cited by 175 · see citing works
Aghajanova, L., Hamilton, A., Kwintkiewicz, J., Vo, K. C., & Giudice, L. C. (2009) · Biology of Reproduction · doi:10.1095/biolreprod.108.070300 · Cited by 168 · see citing works
Epigenetic effects of endocrine-disrupting chemicals on female reproduction: An ovarian perspective
Zama, A. M., & Uzumcu, M. (2010) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2010.06.003 · Cited by 165 · see citing works
The Pathogenesis of Adenomyosis vis-à-vis Endometriosis
Guo, S.-W. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9020485 · Cited by 165 · see citing works
“In addition, ERβ is also hypermethylated and silenced in normal endometrial stromal cells [71].”
BackgroundEstrogen metabolism and action in endometriosis
Rižner, T. L. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.03.022 · Cited by 153 · see citing works
Burns, K. A., Rodriguez, K., Hewitt, S., Janardhan, K., Young, S., & Korach, K. (2012) · Endocrinology · doi:10.1210/en.2012-1294 · Cited by 143 · see citing works
Yamagata, Y., Asada, H., Tamura, I., Lee, L., Maekawa, R., Taniguchi, K., Taketani, T., Matsuoka, A., Tamura, H., & Sugino, N. (2009) · Human Reproduction · doi:10.1093/humrep/dep015 · Cited by 151 · see citing works
Szczepańska, M., Wirstlein, P. K., Skrzypczak, J., & Jagodziński, P. P. (2012) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-10-1 · Cited by 150 · see citing works
Estrogen receptor β: the guardian of the endometrium
Hapangama, D. K., Kamal, A. M., & Bulmer, J. N. (2015) · Human Reproduction Update · doi:10.1093/humupd/dmu053 · Cited by 145 · see citing works
Trukhacheva, E., Lin, Z., Reierstad, S., Cheng, Y.-H., Milad, M., & Bulun, S. E. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1466 · Cited by 143 · see citing works
Self-citationDevelopmental programming: prenatal androgen excess disrupts ovarian steroid receptor balance
Ortega, H. H., Salvetti, N. R., & Padmanabhan, V. (2009) · Reproduction · doi:10.1530/rep-08-0491 · Cited by 133 · see citing works
Mei, J., Zhu, X., Jin, L.-P., Duan, Z., Li, D., & Li, M. (2015) · Human Reproduction · doi:10.1093/humrep/dev100 · Cited by 127 · see citing works
Epigenetic Dysregulation in Endometriosis: Implications for Pathophysiology and Therapeutics
Marquardt, R. M., Tran, D. N., Lessey, B. A., Rahman, M. S., & Jeong, J. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad020 · Cited by 130 · see citing works
Progesterone Receptor Status Predicts Response to Progestin Therapy in Endometriosis
Flores, V. A., Vanhie, A., Dang, T., & Taylor, H. S. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01227 · Cited by 118 · see citing works
Proestling, K., Birner, P., Gamperl, S., Nirtl, N., Márton, E., Yerlikaya‐Schatten, G., Wenzl, R. J., Streubel, B., & Husslein, H. (2015) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-015-0063-7 · Cited by 116 · see citing works
Molecular aspects of development and regulation of endometriosis
Aznaurova, Y. B., M.B.Zhumataev, M. B. Z., Roberts, T. K., Aliper, A. M., & Zhavoronkov, A. A. (2014) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-12-50 · Cited by 116 · see citing works
Lu, Y., Nie, J., Liu, X., Zheng, Y., & Guo, S. (2010) · Human Reproduction · doi:10.1093/humrep/dep472 · Cited by 111 · see citing works
Hayashi, A., Tanabe, A., Kawabe, S., Hayashi, M., Yuguchi, H., Yamashita, Y., Okuda, K., & Ohmichi, M. (2012) · Journal of Ovarian Research · doi:10.1186/1757-2215-5-31 · Cited by 111 · see citing works
Liu, X., Zhang, Q., & Guo, S.-W. (2018) · Reproductive Sciences · doi:10.1177/1933719117718275 · Cited by 110 · see citing works
Estrogen biosynthesis and signaling in endometriosis
Huhtinen, K., Ståhle, M., Perheentupa, A., & Poutanen, M. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.08.022 · Cited by 107 · see citing works
Epithelial Mutations in Endometriosis: Link to Ovarian Cancer
Bulun, S. E., Wan, Y., & Matei, D. E. (2019) · Endocrinology · doi:10.1210/en.2018-00794 · Cited by 103 · see citing works
Self-citationDNA methylation in endometriosis (Review)
KOUKOURA, O., SIFAKIS, S., & SPANDIDOS, D. A. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.4925 · Cited by 103 · see citing works
Endometriosis is characterized by a distinct pattern of histone 3 and histone 4 lysine modifications
Monteiro, J. B., Colón-Díaz, M., García, M., Gutierrez, S., Colón, M., Seto, E., Laboy, J., & Flores, I. (2014) · Reproductive Sciences · doi:10.1177/1933719113497267 · Cited by 98 · see citing works
Han, S. J., & O’Malley, B. W. (2014) · Human Reproduction Update · doi:10.1093/humupd/dmu002 · Cited by 98 · see citing works
Aghajanova, L., Tatsumi, K., Horcajadas, J. A., Zamah, A. M., Esteban, F. J., Herndon, C. N., Conti, M., & Giudice, L. C. (2010) · Biology of Reproduction · doi:10.1095/biolreprod.110.086181 · Cited by 99 · see citing works
Hormonal therapy for endometriosis: from molecular research to bedside
Tosti, C., Biscione, A., Morgante, G., Bifulco, G., Luisi, S., & Petraglia, F. (2017) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2016.05.032 · Cited by 96 · see citing works
Borghese, B., Barbaux, S., Mondon, F., Santulli, P., Pierre, G., Vinci, G., Chapron, C., & Vaiman, D. (2010) · Molecular Endocrinology · doi:10.1210/me.2010-0160 · Cited by 97 · see citing works
Genistein: Dual Role in Women’s Health
Yu, L. C., Rios, E., Castro, L., Liu, J., Yan, Y., & Dixon, D. (2021) · Nutrients · doi:10.3390/nu13093048 · Cited by 94 · see citing works
Cancer-associated mutations in endometriosis: shedding light on the pathogenesis and pathophysiology
Guo, S.-W. (2020) · Human Reproduction Update · doi:10.1093/humupd/dmz047 · Cited by 96 · see citing works
Velarde, M. C., Aghajanova, L., NEZHAT, C. R., & Giudice, L. C. (2009) · Endocrinology · doi:10.1210/en.2009-0389 · Cited by 92 · see citing works
Monsivais, D., Dyson, M. T., Yin, P., Coon, J. S., Navarro, A., Feng, G., Malpani, S. S., Ono, M., Ercan, C. M., Wei, J. J., et al. (2014) · Molecular Endocrinology · doi:10.1210/me.2013-1421 · Cited by 91 · see citing works
Self-citationHypoxia: The force of endometriosis
Wu, M., Hsiao, K., & Tsai, S. (2019) · Journal of Obstetrics and Gynaecology Research · doi:10.1111/jog.13900 · Cited by 88 · see citing works
Nasu, K., Kawano, Y., Tsukamoto, Y., Takano, M., Takai, N., Li, H., Furukawa, Y., Abe, W., Moriyama, M., & Narahara, H. (2011) · Journal of obstetrics and gynaecology research · doi:10.1111/j.1447-0756.2011.01663.x · Cited by 88 · see citing works
Kawano, Y., Nasu, K., Li, H., Tsuno, A., Abe, W., Takai, N., & Narahara, H. (2011) · Human Reproduction · doi:10.1093/humrep/der203 · Cited by 88 · see citing works
Li, Y., Adur, M. K., Kannan, A., Dávila, J., Zhao, Y., Nowak, R. A., Bagchi, M. K., Bagchi, I. C., & Li, Q. (2016) · PLoS ONE · doi:10.1371/journal.pone.0165347 · Cited by 87 · see citing works
Expression Pattern of Stemness-Related Genes in Human Endometrial and Endometriotic Tissues
Forte, A., Schettino, M. T., Finicelli, M., Cipollaro, M., Colacurci, N., Cobellis, L., & Galderisi, U. (2009) · Molecular Medicine · doi:10.2119/molmed.2009.00068 · Cited by 86 · see citing works
The non-human primate model of endometriosis: research and implications for fecundity
Braundmeier, A. G., & Fazleabas, A. T. (2009) · Molecular Human Reproduction · doi:10.1093/molehr/gap057 · Cited by 85 · see citing works
Aromatase and endometriosis: estrogens play a role
Ferrero, S., Remorgida, V., Maganza, C., Venturini, P. L., Salvatore, S., Papaleo, E., Candiani, M., & Maggiore, U. L. R. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12411 · Cited by 84 · see citing works
Yotova, I., Hsu, E., Do, C., Gaba, A., Sczabolcs, M., Dekan, S., Kenner, L., Wenzl, R., & Tycko, B. (2017) · PLOS ONE · doi:10.1371/journal.pone.0170859 · Cited by 81 · see citing works
Local estrogen formation and its regulation in endometriosis
Mori, T., Ito, F., Koshiba, A., Kataoka, H., Takaoka, O., Okimura, H., Khan, K. N., & Kitawaki, J. (2019) · Reproductive Medicine and Biology · doi:10.1002/rmb2.12285 · Cited by 84 · see citing works
Altered genome-wide methylation in endometriosis
Naqvi, H., Ilagan, Y., Krikun, G., & Taylor, H. S. (2014) · Reproductive Sciences · doi:10.1177/1933719114532841 · Cited by 82 · see citing works
Human Endometrial DNA Methylome Is Cycle-Dependent and Is Associated With Gene Expression Regulation
Houshdaran, S., Zelenko, Z., Irwin, J. C., & Giudice, L. C. (2014) · Molecular Endocrinology · doi:10.1210/me.2013-1340 · Cited by 80 · see citing works
Differential regulation of Akt phosphorylation in endometriosis.
Cinar, O., Seval, Y., Uz, Y. H., Cakmak, H., Ulukus, M., Kayisli, U., & Arıcı, A. (2009) · Reproductive Biomedicine Online · doi:10.1016/j.rbmo.2009.10.001 · Cited by 82 · see citing works
Greaves, E., Collins, F., Esnal-Zufiaurre, A., Giakoumelou, S., Horne, A. W., & Saunders, P. T. K. (2014) · Endocrinology · doi:10.1210/en.2014-1086 · Cited by 77 · see citing works
Role of Oxidative Stress in Epigenetic Modification in Endometriosis
Ito, F., Yamada, Y., 重光, 愛., Akinishi, M., Kaniwa, H., Miyake, R., Yamanaka, S., & Kobayashi, H. (2017) · Reproductive Sciences · doi:10.1177/1933719117704909 · Cited by 79 · see citing works
Daidzein-rich isoflavone aglycones inhibit cell growth and inflammation in endometriosis
Takaoka, O., Mori, T., Ito, F., Okimura, H., Kataoka, H., Tanaka, Y., Koshiba, A., Kusuki, I., Shigehiro, S., Amami, T., et al. (2018) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2018.04.004 · Cited by 81 · see citing works
Potential link between estrogen receptor-alpha gene hypomethylation and uterine fibroid formation.
Asada, H., Yamagata, Y., Taketani, T., Matsuoka, A., Tamura, H., Hattori, N., Ohgane, J., Hattori, N., Shiota, K., & Sugino, N. (2008) · Molecular human reproduction · doi:10.1093/molehr/gan045 · Cited by 73 · see citing works
Genome-wide DNA methylation profiling in cultured eutopic and ectopic endometrial stromal cells
Yamagata, Y., Nishino, K., Takaki, E., Sato, S., Maekawa, R., Nakai, A., & Sugino, N. (2014) · PLoS ONE · doi:10.1371/journal.pone.0083612 · Cited by 70 · see citing works
Regulation of estrogen receptor beta activity and implications in health and disease
Swedenborg, E., Power, K. A., Cai, W., Pongratz, I., & Rüegg, J. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0118-z · Cited by 69 · see citing works
The influence of menstrual cycle and endometriosis on endometrial methylome
Saare, M., Modhukur, V., Suhorutshenko, M., Rajashekar, B., Rekker, K., Sõritsa, D., Karro, H., Soplepmann, P., Sõritsa, A., Lindgren, C. M., et al. (2016) · Clinical Epigenetics · doi:10.1186/s13148-015-0168-z · Cited by 68 · see citing works
Liu, M.-H., Liu, X., Zhang, Y., & Guo, S. (2012) · Reproductive Sciences · doi:10.1177/1933719111424453 · Cited by 68 · see citing works
Roy, D., Morgan, M., Yoo, C., Deoraj, A., Roy, S., Yadav, V., Garoub, M. M., Assaggaf, H. M., & Doke, M. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161025285 · Cited by 67 · see citing works
Epigenetic regulation and T-cell responses in endometriosis – something other than autoimmunity
Szukiewicz, D. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.943839 · Cited by 64 · see citing works
Hsiao, K.-Y., Wu, M.-H., Chang, N., Yang, S.-H., Wu, C.-W., Sun, H. S., & Tsai, S.-J. (2015) · Molecular Human Reproduction · doi:10.1093/molehr/gav054 · Cited by 64 · see citing works
van Kaam, K. J. A. F., Delvoux, B., Romano, A., D’Hooghe, T., Dunselman, G. A. J., & Groothuis, P. G. (2011) · Fertility and Sterility · doi:10.1016/j.fertnstert.2011.01.031 · Cited by 64 · see citing works
Machine Learning Classifiers for Endometriosis Using Transcriptomics and Methylomics Data
Akter, S., Xu, D. H., Nagel, S. C., Bromfield, J. J., Pelch, K. E., Wilshire, G., & Joshi, T. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00766 · Cited by 64 · see citing works
Epigenetics of Estrogen and Progesterone Receptors in Endometriosis
Chen, H., Malentacchi, F., Fambrini, M., Harrath, A. H., Huang, H., & Petraglia, F. (2020) · Reproductive Sciences · doi:10.1007/s43032-020-00226-2 · Cited by 66 · see citing works
Monsivais, D., Dyson, M. T., Yin, P., Navarro, A., Coon, J. S., Pavone, M. E., & Bulun, S. E. (2016) · Fertility and Sterility · doi:10.1016/j.fertnstert.2016.01.012 · Cited by 62 · see citing works
Self-citationLi, W.-N., Wu, M., & Tsai, S. (2020) · Reproduction · doi:10.1530/rep-20-0267 · Cited by 62 · see citing works
Forte, A., Cipollaro, M., & Galderisi, U. (2013) · Clinical Science · doi:10.1042/cs20130099 · Cited by 63 · see citing works
Sutrisno, S., Aprina, H., Simanungkalit, H. M., Andriyani, A., Barlıanto, W., Sujuti, H., Santoso, S., Dwijayasa, P. M., Wahyuni, E. S., & Mustofa, E. (2017) · Journal of Traditional and Complementary Medicine · doi:10.1016/j.jtcme.2017.03.002 · Cited by 60 · see citing works
The elusive and controversial roles of estrogen and progesterone receptors in human endometriosis.
Shao, R., Cao, S., Wang, X., Feng, Y., & Billig, H. (2014) · Europe PMC (PubMed Central) · Cited by 55 · see citing works
Expression and regulation of DNA methyltransferases in human endometrium
Vincent, Z. L., Farquhar, C. M., Mitchell, M. D., & Ponnampalam, A. P. (2010) · Fertility and Sterility · doi:10.1016/j.fertnstert.2010.09.030 · Cited by 55 · see citing works
Nothnick, W. B., & Alali, Z. (2016) · F1000Research · doi:10.12688/f1000research.7504.1 · Cited by 55 · see citing works
Ding, Y., Long, C., Liu, X., Chen, X., Guo, L.-R., Xia, Y., He, J., & Wang, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045364 · Cited by 54 · see citing works
Zanatta, A., Pereira, R., da Rocha, A. M., Cogliati, B., Baracat, E. C., Taylor, H. S., Motta, E. L. A., & Serafini, P. C. (2014) · Reproductive Sciences · doi:10.1177/1933719114549846 · Cited by 54 · see citing works
Wang, D., Chen, Q., Zhang, C., Ren, F., & Li, T. (2012) · European journal of medical research · doi:10.1186/2047-783x-17-12 · Cited by 53 · see citing works
Logan, P. C., Yango, P., & Tran, N. D. (2017) · Reproductive Sciences · doi:10.1177/1933719117704905 · Cited by 54 · see citing works
Endometriosis research in the -omics era
Goulielmos, G. N., Matalliotakis, M., Matalliotaki, C., Eliopoulos, E., Matalliotakis, I., & Zervou, M. I. (2020) · Gene · doi:10.1016/j.gene.2020.144545 · Cited by 49 · see citing works
Epigenetic aberration of gene expression in endometriosis
Izawa, M. (2013) · Frontiers in Bioscience · doi:10.2741/e669 · Cited by 49 · see citing works
Arosh, J. A., Lee, J., Starzinski‐Powitz, A., & Banu, S. K. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.03.023 · Cited by 49 · see citing works
Xenoestrogen regulation of ERα/ERβ balance in hormone-associated cancers
Acconcia, F., Fiocchetti, M., & Marino, M. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.10.033 · Cited by 49 · see citing works
Gołąbek-Grenda, A., & Olejnik, A. M. (2022) · Cellular Signalling · doi:10.1016/j.cellsig.2022.110375 · Cited by 48 · see citing works
- Authors
- Xue, Q., Lin, Z., Cheng, Y.-H., Huang, C.-C., Marsh, E., Yin, P., Milad, M. P., Confino, E., Reierstad, S., Innes, J., & Bulun, S. E.
- Affiliations
- Northwestern University (US)
- Peking University (CN)
- Corresponding author
- Bulun, Serdar E.
- Venue
- Biology of Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-10-01
- Volume
- 77
- Issue
- 4
- Pages
- 681-687
- ISSN
- 0006-3363 (ISSN-L)
- 1529-7268
- OpenAlex
- W2164434026
- Cited by
- 346
- References
- 43
- Citations by year
- 2026: 15 · 2025: 13 · 2024: 20 · 2023: 30 · 2022: 19 · 2021: 24 · 2020: 23 · 2019: 25 · 2018: 16 · 2017: 15 · 2016: 14 · 2015: 22 · 2014: 27 · 2013: 14 · 2012: 24
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biology of Reproduction (publishedVersion)
- PubMed (publishedVersion)
- BioOne Complete (BioOne) (submittedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD040093, U54-HD40093)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- estrogen receptor 2, endometriosis, endometrium, DNA methylation, promoter methylation, CpG islands, endometrial stromal cells, estrogen receptor 1, progesterone receptor, gene expression regulation, decitabine, promoter deletion mutants
- MeSH terms
- Decitabine, Adult, Azacitidine, Cells, Cultured, Endometriosis, Endometrium, Female, Gene Expression Regulation, Humans, Promoter Regions, Genetic, Receptors, Progesterone, RNA, Messenger, Stromal Cells, CpG Islands, DNA Methylation, Estrogen Receptor alpha, Estrogen Receptor beta
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