The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Estrogen Receptor β Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis
Open accessAbstract
Alterations in estrogen-mediated cellular signaling play an essential role in the pathogenesis of endometriosis. In addition to higher estrogen receptor (ER) β levels, enhanced ERβ activity was detected in endometriotic tissues, and the inhibition of enhanced ERβ activity by an ERβ-selective antagonist suppressed mouse ectopic lesion growth. Notably, gain of ERβ function stimulated the progression of endometriosis. As a mechanism to evade endogenous immune surveillance for cell survival, ERβ interacts with cellular apoptotic machinery in the cytoplasm to inhibit TNF-α-induced apoptosis. ERβ also interacts with components of the cytoplasmic inflammasome to increase interleukin-1β and thus enhance its cellular adhesion and proliferation properties. Furthermore, this gain of ERβ function enhances epithelial-mesenchymal transition signaling, thereby increasing the invasion activity of endometriotic tissues for establishment of ectopic lesions. Collectively, we reveal how endometrial tissue generated by retrograde menstruation can escape immune surveillance and develop into sustained ectopic lesions via gain of ERβ function.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Aberrantly high ESR2 levels regulate several pathological processes in endometriotic tissue including proliferation, inhibition of apoptosis, inflammation and pain transmission”
From Endometriosis and nuclear receptors (2019) · cites this paper as Han et al., 2015
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The inhibition of ESR2 activity by an ESR2-selective estrogen antagonist suppresses lesion growth in these animals, whereas gain of ESR2 function stimulates the progression of endometriosis”
From Endometriosis and nuclear receptors (2019) · cites this paper as Han et al., 2015
In the citing paper
“ERβ is the predominant isoform in patients with endometriosis [7,8].”
From Polymorphisms in the 3 ′ UTR Region of ESR2 and CYP19A1 Genes and Its Influence on Allele-Specific Gene Expression in Endometriosis (2020) · cites this paper as [8]
In the citing paper
“Progesterone resistance may of course explain this unexpected issue [18,19,20,21,22].”
From Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review (2021) · cites this paper as [19]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes
Micheau, O., & Tschopp, J. (2003) · Cell · doi:10.1016/s0092-8674(03)00521-x · Cited by 2,738
Giudice, L. C. (2010) · New England Journal of Medicine · doi:10.1056/nejmcp1000274 · Cited by 1,924
Bulun, S. E. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0804690 · Cited by 1,772
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 1,717
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
ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis
Tobiume, K., Matsuzawa, A., Takahashi, T., Nishitoh, H., Morita, K., Takeda, K., Minowa, O., Miyazono, K., Noda, T., & Ichijo, H. (2001) · EMBO Reports · doi:10.1093/embo-reports/kve046 · Cited by 1,211
Caspase‐1‐induced pyroptotic cell death
Miao, E. A., Rajan, J. V., & Aderem, A. A. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01044.x · Cited by 1,162
Impact of endometriosis on women’s lives: a qualitative study
Moradi, M., Parker, M. A., Sneddon, A., López, V., & Ellwood, D. A. (2014) · BMC Women s Health · doi:10.1186/1472-6874-14-123 · Cited by 525
Progesterone 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
Regulation of the Apaf-1–caspase-9 apoptosome
Bratton, S. B., & Salvesen, G. S. (2010) · Journal of Cell Science · doi:10.1242/jcs.073643 · Cited by 434
Pathophysiology and Immune Dysfunction in Endometriosis
Ahn, S. H., Monsanto, S. P., Miller, C. D., Singh, S. S., Thomas, R., & Tayade, C. (2015) · BioMed Research International · doi:10.1155/2015/795976 · Cited by 413
Cre-mediated recombination in cell lineages that express the progesterone receptor
Soyal, S. M., Mukherjee, A., Lee, K. Y.-S., Li, J., Li, H., DeMayo, F. J., & Lydon, J. P. (2005) · genesis · doi:10.1002/gene.20098 · Cited by 380
Self-citationTobiume, K., Saitoh, M., & Ichijo, H. (2002) · Journal of Cellular Physiology · doi:10.1002/jcp.10080 · Cited by 362
Estrogen receptors α and β in the rodent mammary gland
Saji, S., Jensen, E. V., Nilsson, S. V., Rylander‐Rudqvist, T., Warner, M. N., & Gustafsson, J.-Α. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.1.337 · Cited by 357
Endometriosis: cost estimates and methodological perspective
Simoens, S., Hummelshoj, L., & D'Hooghe, T. (2007) · Human Reproduction Update · doi:10.1093/humupd/dmm010 · Cited by 357
Willingham, S. B., Allen, I. C., Bergstralh, D. T., Brickey, W. J., Huang, M. T.-H., Taxman, D. J., Duncan, J. A., & Ting, J. P. ‐. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900138 · Cited by 356
Ligand-independent activation of steroid hormone receptors
Weigel, N. L., & Zhang, Y. (1998) · Journal of Molecular Medicine · doi:10.1007/s001090050241 · Cited by 351
Endometriosis and Infertility: Epidemiology and Evidence‐based Treatments
Ozkan, S., Murk, W., & Arici, A. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1434.007 · Cited by 347
Promoter Methylation Regulates Estrogen Receptor 2 in Human Endometrium and Endometriosis1
Xue, Q., Lin, Z., Cheng, Y.-H., Huang, C.-C., Marsh, E., Yin, P., Milad, M. P., Confino, E., Reierstad, S., Innes, J., et al. (2007) · Biology of Reproduction · doi:10.1095/biolreprod.107.061804 · Cited by 346
Hatai, T., Matsuzawa, A., Inoshita, S., Mochida, Y., Kuroda, T., Sakamaki, K., Kuida, K., Yonehara, S., Ichijo, H., & Takeda, K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003412200 · Cited by 332
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 321
A Novel Immortalized Human Endometrial Stromal Cell Line with Normal Progestational Response
Krikun, G., Mor, G., Alvero, A. B., Guller, S. M., Schatz, F., Sapi, E., Rahman, M. M., Caze, R., Qumsiyeh, M. Β., & Lockwood, C. J. (2004) · Endocrinology · doi:10.1210/en.2003-1606 · Cited by 285
Holoch, K., & Lessey, B. A. (2010) · Clinical Obstetrics & Gynecology · doi:10.1097/grf.0b013e3181db7d71 · Cited by 264
Compton, D. R., Sheng, S., Carlson, K. E., Rebacz, N. A., Lee, I. Y., Katzenellenbogen, B. S., & Katzenellenbogen, J. A. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm049631k · Cited by 184
Dual suppression of estrogenic and inflammatory activities for targeting of endometriosis
Zhao, Y., Gong, P., Chen, Y., Nwachukwu, J. C., Srinivasan, S., Ko, C., Bagchi, M. K., Taylor, R. N., Korach, K. S., Nettles, K. W., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.3010626 · Cited by 170
Vanderschueren, D., Herck, E. V., Nijs, J., EDERVEEN, A. G. H., Coster, R. D., & Bouillon, R. (1997) · Endocrinology · doi:10.1210/endo.138.6.5216 · Cited by 151
Han, S. J., Hawkins, S. M., Begum, K., Jung, S. Y., Kovanci, E., Qin, J., Lydon, J. P., DeMayo, F. J., & O'Malley, B. W. (2012) · Nature Medicine · doi:10.1038/nm.2826 · Cited by 149
Self-citationWei, Q., Guo, P., Mu, K., Zhang, Y., Zhao, W., Huai, W., Qiu, Y., Li, T., Ma, X., Liu, Y., et al. (2015) · Laboratory Investigation · doi:10.1038/labinvest.2015.63 · Cited by 146
Pellegrini, C., Gori, I., Achtari, C., Hornung, D., Chardonnens, E., Wunder, D. M., Fiche, M., & Canny, G. (2012) · Fertility and Sterility · doi:10.1016/j.fertnstert.2012.06.056 · Cited by 144
Burns, K. A., Rodriguez, K., Hewitt, S., Janardhan, K., Young, S., & Korach, K. (2012) · Endocrinology · doi:10.1210/en.2012-1294 · Cited by 143
Compton, D. R., Sheng, S., Carlson, K. E., Rebacz, N. A., Lee, I. Y., Katzenellenbogen, B. S., & Katzenellenbogen, J. A. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm058162z · Cited by 137
Estrogen Receptor Knockout Mice as a Model for Endocrine Research
Walker, V. R., & Korach, K. S. (2004) · ILAR Journal · doi:10.1093/ilar.45.4.455 · Cited by 128
Increased Production of 17β-Estradiol in Endometriosis Lesions Is the Result of Impaired Metabolism
Delvoux, B., Groothuis, P. G., D’Hooghe, T. M., Kyama, C. M., Dunselman, G. A. J., & Romano, A. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-2218 · Cited by 123
Small Molecule Inhibition of the Steroid Receptor Coactivators, SRC-3 and SRC-1
Wang, Y., Lonard, D. M., Yu, Y., Chow, D., Palzkill, T. G., & O’Malley, B. W. (2011) · Molecular Endocrinology · doi:10.1210/me.2011-1222 · Cited by 122
Self-citationHarris, 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
Han, S. J., & O’Malley, B. W. (2014) · Human Reproduction Update · doi:10.1093/humupd/dmu002 · Cited by 98
Self-citationMonsivais, 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
Cao, W. G., Morin, M., Metz, C. N., Maheux, R., & Akoum, A. (2005) · Biology of Reproduction · doi:10.1095/biolreprod.104.038331 · Cited by 91
17βE2 promotes cell proliferation in endometriosis by decreasing PTEN via NFκB-dependent pathway
Zhang, H., Ζhao, X., Liu, S., Li, J., Wen, Z., & Li, M. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.11.009 · Cited by 85
Cheng, C., Licence, D. R., Cook, E., Luo, F., Arends, M. J., Smith, S. K., Print, C. G., & Jones, D. S. (2011) · The Journal of Pathology · doi:10.1002/path.2852 · Cited by 63
Sillem, M., Prifti, S., Monga, B., Arslic‐Schmitt, T., & Runnebaum, B. (1999) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/s0301-2115(99)00114-1 · Cited by 56
Creation of immortalised epithelial cells from ovarian endometrioma
Bono, Y., Kyo, S., Takakura, M., Maida, Y., Mizumoto, Y., Nakamura, M., Nomura, K., Kiyono, T., & Inoue, M. (2012) · British Journal of Cancer · doi:10.1038/bjc.2012.26 · Cited by 55
Self-citationInvolvement of resistance to apoptosis in the pathogenesis of endometriosis.
Nasu, K., Yuge, A., Tsuno, A., Nishida, M., & Narahara, H. (2009) · PubMed · doi:10.14670/hh-24.1181 · Cited by 46
Acién, P., Velasco, I., Gutiérrez, M., & Martínez-Beltrán, M. (2007) · Fertility and Sterility · doi:10.1016/j.fertnstert.2006.11.188 · Cited by 41
The genetics and biochemistry of endometriosis
Burney, R. O. (2013) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0b013e3283630d56 · Cited by 34
Danazol and benign intracranial hypertension.
Shah, A. M., Roberts, T., McQueen, I. N., Graham, J., & Walker, K. (1987) · BMJ · doi:10.1136/bmj.294.6583.1323 · Cited by 27
Apoptosis Resistance in Endometriosis
Salmassi, A., Acar-Perk, B., Schmutzler, A. G., Koch, K., Püngel, F., Jonat, W., & Mettler, L. (2011) · Europe PMC (PubMed Central) · doi:10.5681/bi.2011.017 · Cited by 10
An estrogen receptor alpha activity indicator model in mice
Han, S. J., O’Malley, B. W., & DeMayo, F. J. (2009) · genesis · doi:10.1002/dvg.20572 · Cited by 9
Self-citationENDOMETRIOSIS AND RETROGRADE MENSTRUATION Case Report and Review
Hughesdon, P. E. (1958) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1958.tb08588.x · Cited by 7
Endometriosis and retrograde menstruation
Kruitwagen, R. F. P. M. (1991) · Radboud Repository (Radboud University) · Cited by 3
Cited by
Sorted by citations
Zondervan, K. T., Becker, C. M., & Missmer, S. A. (2020) · New England Journal of Medicine · doi:10.1056/nejmra1810764 · Cited by 2,249
Zondervan, K. T., Becker, C. M., Koga, K., Missmer, S. A., Taylor, R. N., & Viganò, P. (2018) · Nature Reviews Disease Primers · doi:10.1038/s41572-018-0008-5 · Cited by 1,257
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
The Immunopathophysiology of Endometriosis
Symons, L. K., Miller, J. E., Kay, V. R., Marks, R. M., Liblik, K., Koti, M., & Tayade, C. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.07.004 · Cited by 601
Progesterone 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 527
Metadata
- Authors
- 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., DeMayo, F. J., & O’Malley, B. W.
- Affiliations
- Baylor College of Medicine (US)
- Kanazawa University (JP)
- Corresponding author
- O’Malley, Bert W.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 163
- Issue
- 4
- Pages
- 960-974
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4640214
- OpenAlex
- W2169528901
- Cited by
- 380
- References
- 51
- Citations by year
- 2026: 29 · 2025: 40 · 2024: 42 · 2023: 47 · 2022: 40 · 2021: 41 · 2020: 42 · 2019: 38 · 2018: 28 · 2017: 15 · 2016: 17 · 2015: 1
- FWCI
- 23.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P30CA123125)
- National Institute of Diabetes and Digestive and Kidney Diseases (U19 DK-62434, P01DK059820, U19DK062434)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54 HD-0077495, R01HD082786, R01HD07857, R01HD08188, U54HD007495, R01HD042311, R03HD077495, K12HD050128, R01HD008188, R01HD007857)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Health Sciences › Medicine › Obstetrics and Gynecology › Ectopic Pregnancy Diagnosis and Management
- Keywords
- endometriosis, estrogen receptor beta, apoptosis, inflammasome, IL-1β, TNF-induced apoptosis, epithelial-mesenchymal transition, immune evasion, retrograde menstruation, ectopic lesions
- MeSH terms
- Animals, Cell Adhesion, Endometriosis, Female, Humans, Immunologic Surveillance, Menstruation, Tumor Necrosis Factor-alpha, Apoptosis, Estrogen Receptor alpha, Estrogen Receptor beta, Cell Proliferation, Mice, Interleukin-1beta, Inflammasomes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
