Epithelial to mesenchymal transition-like and mesenchymal to epithelial transition-like processes might be involved in the pathogenesis of pelvic endometriosis†
Abstract
BACKGROUND: Endometrium is derived from intermediate mesoderm via mesenchymal to epithelial transition (MET) during development of the urogenital system. By retaining some imprint of their mesenchymal origin, endometrial epithelial cells may be particularly prone to return to this state, via epithelial to mesenchymal transition (EMT). We hypothesized that pelvic endometriosis originates from retrograde menstruation of endometrial tissue and that EMT-like and MET-like processes might be involved in the pathogenesis of pelvic endometriosis. METHODS: We investigated commonly used molecular markers for EMT, including cytokeratin, E-cadherin, N-cadherin, vimentin, S100A4 and dephosphorylated beta-catenin by immunohistochemistry in different forms of pelvic endometriosis: deep infiltrating endometriosis, ovarian endometriosis and superficial peritoneal endometriosis (red and black lesions), as well as samples of menstrual endometrium, other benign ovarian cysts (mucinous and serous cyst adenoma), and abdominal scar endometriosis for comparison. RESULTS: Epithelial cells of red peritoneal lesions and ovarian endometriosis showed less epithelial marker (cytokeratin, P < 0.0001) expression and more mesenchymal marker (vimentin and/or S100A4, P < 0.0001) expression than those of menstrual endometrium. In contrast, epithelial cells of black peritoneal lesions and deep infiltrating endometriosis showed more epithelial marker (E-cadherin) expression than those of menstrual endometrium (P < 0.03), red peritoneal lesions (P < 0.0001) and ovarian endometriosis (P< 0.0001), but maintained expression of some mesenchymal markers (vimentin, S100A4). In addition, dephosphorylated beta-catenin protein expression was significantly higher in epithelial cells of deep infiltrating endometriosis (P < 0.0001) than in epithelial cells of red and black peritoneal lesions and ovarian endometriosis. CONCLUSIONS: EMT-like and MET-like processes might be involved in the pathogenesis of pelvic endometriosis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
During epithelial-mesenchymal transition, it is possible to reach the formation of foci of endometriosis.
“It is a reversible process, therefore, during the epithelial-mesenchymal transition (EMT, reverse process MET), it is possible to reach the formation of foci of endometriosis [145].”
From Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature) (2021) · cites this paper as [145]
Cites
Epithelial-Mesenchymal Transitions in Development and Disease
Thiery, J. P., Acloque, H., Huang, R. Y. J., & Nieto, M. A. (2009) · Cell · doi:10.1016/j.cell.2009.11.007 · Cited by 9,931 · see citing works
Epithelial–mesenchymal transitions in tumour progression
Thiery, J. P. (2002) · Nature reviews. Cancer · doi:10.1038/nrc822 · Cited by 6,632 · see citing works
Wnt/β-Catenin Signaling in Development and Disease
Clevers, H. (2006) · Cell · doi:10.1016/j.cell.2006.10.018 · Cited by 5,568 · 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
Revised American Society for Reproductive Medicine classification of endometriosis: 1996
American Society for Reproductive Medicine (1997) · Fertility and Sterility · doi:10.1016/s0015-0282(97)81391-x · Cited by 3,018 · see citing works
Epithelial-mesenchymal transition and its implications for fibrosis
Kalluri, R., & Neilson, E. G. (2003) · Journal of Clinical Investigation · doi:10.1172/jci20530 · Cited by 2,651 · see citing works
The epithelial–mesenchymal transition: new insights in signaling, development, and disease
Lee, J. M., Dedhar, S., Kalluri, R., & Thompson, E. W. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200601018 · Cited by 2,018 · see citing works
The Origin and Pathogenesis of Epithelial Ovarian Cancer: A Proposed Unifying Theory
Kurman, R. J., & Shih, I. (2010) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e3181cf3d79 · Cited by 1,850 · see citing works
Evidence that fibroblasts derive from epithelium during tissue fibrosis
Iwano, M., Plieth, D., Danoff, T. M., Xue, C., Okada, H., & Neilson, E. G. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15518 · Cited by 1,809 · see citing works
WNT and β-catenin signalling: diseases and therapies
Moon, R. T., Kohn, A. D., Ferrari, G. V. D., & Kaykas, A. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1427 · Cited by 1,763 · see citing works
Burk, U., Schubert, J., Wellner, U. F., Schmalhofer, O., Vincan, E., Spaderna, S., & Brabletz, T. (2008) · EMBO Reports · doi:10.1038/embor.2008.74 · Cited by 1,722 · 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
Evidence that fibroblasts derive from epithelium during tissue fibrosis
Iwano, M., Plieth, D., Danoff, T. M., Xue, C., Okada, H., & Neilson, E. G. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215518 · Cited by 1,589 · see citing works
Blaustein's Pathology of the Female Genital Tract
Kurman, R. J., Ellenson, L. H., & Ronnett, B. M. (2019) · Springer eBooks · doi:10.1007/978-3-319-46334-6 · Cited by 1,338 · see citing works
Nisolle, M., & Donnez, J. (1997) · Fertility and Sterility · doi:10.1016/s0015-0282(97)00191-x · Cited by 1,279 · see citing works
Epithelial—mesenchymal and mesenchymal—epithelial transitions in carcinoma progression
Hugo, H. J., Ackland, M. L., Blick, T., Lawrence, M. G., Clements, J. A., Williams, E. D., & Thompson, E. W. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21223 · Cited by 1,091 · see citing works
Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer—Shifting the paradigm
Kurman, R. J., & Shih, I. (2011) · Human Pathology · doi:10.1016/j.humpath.2011.03.003 · Cited by 1,076 · see citing works
Wnt Signaling Controls the Phosphorylation Status of β-Catenin
van Noort, M., Meeldijk, J., van der Zee, R., Destrée, O., & Clevers, H. C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111635200 · Cited by 468 · see citing works
Donnez, J., Nisolle, M., Gillet, N., Smets, M., Bassil, S., & Casanas-Roux, F. (1996) · Human Reproduction · doi:10.1093/humrep/11.3.641 · Cited by 360 · cited 1× · see citing works
“However, the present study revealed significantly lower expression of vimentin in ovarian endometriosis compared with peritoneal and deep infiltrating lesions, in agreement with the results of a previous analysis by Donnez et al. (1996).”
ResultWells, A. H., Yates, C. C., & Shepard, C. R. (2008) · Clinical & Experimental Metastasis · doi:10.1007/s10585-008-9167-1 · Cited by 353 · see citing works
Özcan, A., Shen, S. S., Hamilton, C., Anjana, K., Coffey, D., Krishnan, B., & Truong, L. D. (2011) · Modern Pathology · doi:10.1038/modpathol.2011.3 · Cited by 344 · see citing works
Zeitvogel, A., Baumann, R., & Starzinski‐Powitz, A. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63030-1 · Cited by 275 · see citing works
Wnt/β-Catenin and Estrogen Signaling Converge in Vivo
Kouzmenko, A., Takeyama, K., Ito, S., Furutani, T., Sawatsubashi, S., Maki, A., Suzuki, E., Kawasaki, Y., Akiyama, T., Tabata, T., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c400331200 · Cited by 214 · see citing works
Endometrial-Peritoneal Interactions during Endometriotic Lesion Establishment
Hull, M. L., Rangel‐Escareño, C., Godsland, J. M., Doig, J. R., Johnson, C. M., Phillips, S. C., Smith, S. K., Tavaré, S., Print, C. G., & Jones, D. S. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2008.071128 · Cited by 174 · see citing works
Gaetje, R., Kotzian, S., Herrmann, G., BAUMANN, R., & Starzinski‐Powitz, A. (1997) · Europe PMC (PubMed Central) · Cited by 144 · see citing works
Progesterone Inhibition of Wnt/β-Catenin Signaling in Normal Endometrium and Endometrial Cancer
Wang, Y., Hanifi‐Moghaddam, P., Hanekamp, E. E., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-0814 · Cited by 138 · see citing works
Clement, P. B. (1994) · Springer eBooks · doi:10.1007/978-1-4757-3889-6_17 · Cited by 129 · see citing works
Matsuzaki, S., Canis, M. J., Darcha, C., Pouly, J. L., & Mage, G. (2009) · Human Reproduction · doi:10.1093/humrep/dep306 · Cited by 121 · see citing works
Self-citationA Modified Baboon Model for Endometriosis
Fazleabas, A. T., Brudney, A., Gürateş, B., Chai, D. C., & Bulun, S. E. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb02791.x · Cited by 120 · see citing works
Matsuzaki, S., Darcha, C., Maleysson, E., Canis, M. J., & Mage, G. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2713 · Cited by 116 · see citing works
Self-citationEmbryologic origin of endometriosis: Analysis of 101 human female fetuses
Signorile, P. G., Baldi, F., Bussani, R., Viceconte, R., Bulzomi, P., D'Armiento, M., D’Avino, A., & Baldi, A. (2011) · Journal of Cellular Physiology · doi:10.1002/jcp.22888 · Cited by 105 · see citing works
Essential roles of mesenchyme-derived beta-catenin in mouse Müllerian duct morphogenesis
Deutscher, E., & Yao, H. H. (2007) · Developmental Biology · doi:10.1016/j.ydbio.2007.04.036 · Cited by 99 · see citing works
Plasma membrane recruitment of dephosphorylated β-catenin upon activation of the Wnt pathway
Hendriksen, J., Jansen, M., Brown, C. M., van der Velde, H., van Ham, M., Galjart, N., Offerhaus, G. J. A., Fagotto, F., & Fornerod, M. W. J. (2008) · Journal of Cell Science · doi:10.1242/jcs.025536 · Cited by 76 · see citing works
New evidence of the presence of endometriosis in the human fetus
Signorile, P. G., Baldi, F., Bussani, R., D’Armiento, M., De Falco, M., Boccellino, M., Quagliuolo, L., & Baldi, A. (2010) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2010.04.002 · Cited by 65 · cited 2× · see citing works
“They further proposed that ectopic endometrium would remain quiescent until puberty, at which time hormonal signals would stimulate its growth (Signorile et al., 2010, 2011).”
BackgroundMatsuzaki, S., Maleysson, E., & Darcha, C. (2009) · Human Reproduction · doi:10.1093/humrep/dep435 · Cited by 59 · see citing works
Self-citationHypomethylation-induced expression of S100A4 in endometrial carcinoma
Xie, R., Loose, D. S., Shipley, G. L., et al. (2007) · Modern Pathology · doi:10.1038/modpathol.3800940 · Cited by 53 · see citing works
Nisolle, M., Casanas‐Roux, F., & Donnez, J. (1995) · Fertility and Sterility · doi:10.1016/s0015-0282(16)57657-2 · Cited by 37 · see citing works
Endometriosis may be generated by mimicking the ontogenetic development of the female genital tract
Gaetje, R., Holtrich, U., Engels, K., Kissler, S., Rody, A., Karn, T., & Kaufmann, M. (2006) · Fertility and Sterility · doi:10.1016/j.fertnstert.2006.07.1533 · Cited by 34 · see citing works
Charpin, C., Devictor, B., Bonnier, P., et al. (1993) · The Journal of Pathology · doi:10.1002/path.1711700410 · Cited by 26 · see citing works
Patten, K. V., Parkash, V., & Jain, D. (2009) · Modern Pathology · doi:10.1038/modpathol.2009.127 · Cited by 22 · see citing works
Clement, P. B. (1994) · Medical Entomology and Zoology · Cited by 21 · see citing works
Distribution of vimentin in the developing chick taste bud during the perihatching period.
Witt, M., Ganchrow, J. R., & Ganchrow, D. (1999) · PubMed · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
Smolarz, B., Szyłło, K., & Romanowicz, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910554 · Cited by 560 · see citing works
Zhang, Q., Duan, J., Liu, X., & Guo, S.-W. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.03.015 · Cited by 211 · see citing works
MicroRNA expression profile in endometriosis: its relation to angiogenesis and fibrinolytic factors
Braza-Boïls, A., Marí-Alexandre, J., Gilabert, J., Sánchez-Izquierdo, D., España, F., Estellés, A., & Gilabert-Estellés, J. (2014) · Human Reproduction · doi:10.1093/humrep/deu019 · Cited by 164 · see citing works
Matsuzaki, S., & Darcha, C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076808 · Cited by 138 · see citing works
Self-citationCancer-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
Guo, S.-W., Ding, D., Shen, M., & Liu, X. (2015) · Reproductive Sciences · doi:10.1177/1933719115570907 · Cited by 86 · see citing works
Endometriosis and adenomyosis: Similarities and differences
Donnez, J., Stratopoulou, C. A., & Dolmans, M.-M. (2024) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2023.102432 · Cited by 57 · see citing works
Liu, H., Du, Y., Zhang, Z., Lv, L., Xiong, W., Zhang, L., Li, N., He, H., Li, Q., & Liu, Y. (2018) · Biology of Reproduction · doi:10.1093/biolre/ioy128 · Cited by 53 · see citing works
The establishment of a mouse model of deep endometriosis
Yan, D., Liu, X., & Guo, S.-W. (2019) · Human Reproduction · doi:10.1093/humrep/dey361 · Cited by 47 · see citing works
Liao, T.-L., Lee, Y.-C., Tzeng, C.-R., Wang, Y.-P., Chang, H.-Y., Lin, Y.-F., & Kao, S.-H. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.01.022 · Cited by 44 · see citing works
Endometrioma in abdominal scars: case reports of four cases and review of the literature
Uysal, A., Mun, S., & Taner, C. E. (2012) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-012-2320-8 · Cited by 10 · see citing works
Endometriosis and aspirin: a systematic review
Yang, Y., Lai, H., Li, Z., & Zhang, J. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1409469 · Cited by 7 · see citing works
- Authors
- Matsuzaki, S., & Darcha, C.
- Affiliations
- Centre Hospitalier Universitaire de Clermont-Ferrand (FR)
- Venue
- Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-01-02
- Volume
- 27
- Issue
- 3
- Pages
- 712-721
- ISSN
- 0268-1161 (ISSN-L)
- 1460-2350
- OpenAlex
- W2171875732
- Cited by
- 216
- References
- 42
- Citations by year
- 2026: 5 · 2025: 17 · 2024: 14 · 2023: 15 · 2022: 16 · 2021: 23 · 2020: 23 · 2019: 13 · 2018: 21 · 2017: 18 · 2016: 14 · 2015: 16 · 2014: 10 · 2013: 8 · 2012: 3
- FWCI
- 13.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Plant and fungal interactions
- Keywords
- epithelial-mesenchymal transition, mesenchymal-epithelial transition, endometriosis pathogenesis, retrograde menstruation, deep infiltrating endometriosis, endometrioma, peritoneal endometriosis, E-cadherin, N-cadherin, vimentin, S100A4, cytokeratin, endometrial epithelial cells
- MeSH terms
- S100 Calcium-Binding Protein A4, Adult, Cell Differentiation, Cicatrix, Endometriosis, Epithelial Cells, Female, Humans, Keratins, Menstrual Cycle, S100 Proteins, Ovarian Cysts, Vimentin, Biomarkers, Cadherins, beta Catenin, Epithelial-Mesenchymal Transition
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