{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T03:28:26Z","timestamp":1788406106400,"version":"build-2803163510"},"reference-count":11,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondation Saint-Luc","award":["PDR T.0171.21"],"award-info":[{"award-number":["PDR T.0171.21"]}]},{"DOI":"10.13039\/501100002661","name":"Fonds National de la Recherche Scientifique de Belgique (FNRS)","doi-asserted-by":"publisher","award":["PDR T.0171.21"],"award-info":[{"award-number":["PDR T.0171.21"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Adenomyosis is a benign gynecological disorder associated with abnormal uterine bleeding, dysmenorrhea, and subfertility. Its pathogenesis has not yet been elucidated. The most widely accepted theory points to repeated mechanical or hormonal stress at the endometrial\u2013myometrial interface, leading to activation of the tissue injury and repair (TIAR) mechanism. Studies suggest that the immune system may play a role in disease pathogenesis, but inconsistencies persist due to differences in studied samples and evaluated menstrual cycle phases. The goal of our study was to apply a novel technique (multiplex) to investigate different immune cell phenotypes in uteri from adenomyosis patients according to the cycle phase. Methods: This study analyzed immune cell populations in adenomyotic uteri using immunohistochemistry and multiplex immunofluorescence on 30 adenomyotic and 15 healthy hysterectomy samples. Results: Compared to eutopic endometrium, transitional and adenomyotic lesions displayed reduced immune infiltrates, particularly T cells, NK cells, B cells, macrophages, and dendritic cells. Conversely, mast cells were significantly elevated in transitional lesions. Conclusions: The present study suggests mast cell implication in adenomyosis development and pain, through their implication in tissue remodeling, angiogenesis, and neurogenic inflammation. Transitional lesions highlighted the progressive nature of adenomyosis, supporting the TIAR hypothesis. These findings emphasize the importance of mast cells in disease progression and underscore the need for further studies to explore immune-targeted therapies.<\/jats:p>","DOI":"10.3390\/jcm14134578","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T13:06:17Z","timestamp":1751288777000},"page":"4578","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Transitional Lesions, One More Step Towards Understanding the Pathogenesis of Adenomyosis"],"prefix":"10.3390","volume":"14","author":[{"given":"Emilie","family":"Wacheul","sequence":"first","affiliation":[{"name":"Gynecology Research Unit, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"},{"name":"Anatomopathology Department, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6331-3026","authenticated-orcid":false,"given":"Marie-Madeleine","family":"Dolmans","sequence":"additional","affiliation":[{"name":"Gynecology Research Unit, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"},{"name":"Gynecology Department, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1218-6143","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Ambroise","sequence":"additional","affiliation":[{"name":"Centre des Technologies Mol\u00e9culaires Appliqu\u00e9es (CTMA), Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2528-206X","authenticated-orcid":false,"given":"Jacques","family":"Donnez","sequence":"additional","affiliation":[{"name":"Society for Research into Infertility, 1150 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Camboni","sequence":"additional","affiliation":[{"name":"Gynecology Research Unit, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"},{"name":"Anatomopathology Department, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Camboni, A., and Marbaix, E. (2021). Ectopic Endometrium: The Pathologist\u2019s Perspective. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222010974"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1007\/s43032-020-00361-w","article-title":"Origin and Pathogenic Mechanisms of Uterine Adenomyosis: What Is Known So Far","volume":"28","author":"Stratopoulou","year":"2021","journal-title":"Reprod. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.fertnstert.2017.12.030","article-title":"Pathogenesis of Uterine Adenomyosis: Invagination or Metaplasia?","volume":"109","author":"Donnez","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"103925","DOI":"10.1016\/j.jri.2023.103925","article-title":"Characterising the Immune Cell Phenotype of Ectopic Adenomyosis Lesions Compared with Eutopic Endometrium: A Systematic Review","volume":"157","author":"Maclean","year":"2023","journal-title":"J. Reprod. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1093\/humupd\/dmaa038","article-title":"Immunological Changes Associated with Adenomyosis: A Systematic Review","volume":"27","author":"Bourdon","year":"2021","journal-title":"Human Reprod. Update"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.fertnstert.2018.01.024","article-title":"Role of transvaginal sonography and magnetic resonance imaging in the diagnosis of uterine adenomyosis","volume":"109","author":"Bazot","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref_7","first-page":"e65220","article-title":"Multiplex Immunofluorescence Combined with Spatial Image Analysis for the Clinical and Biological Assessment of the Tumor Microenvironment","volume":"196","author":"Huyghe","year":"2023","journal-title":"J. Vis. Exp."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1080\/14728222.2017.1260548","article-title":"Targeting Mast Cells: A New Way to Treat Endometriosis","volume":"21","author":"Binda","year":"2017","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1016\/j.fertnstert.2006.03.057","article-title":"Pain, mast cells, and nerves in peritoneal, ovarian, and deep infiltrating endometriosis","volume":"86","author":"Anaf","year":"2006","journal-title":"Fertil. Steril."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"224","DOI":"10.7150\/ijms.39252","article-title":"The New Application of Mifepristone in the Relief of Adenomyosis-Caused Dysmenorrhea","volume":"17","author":"Che","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Habiba, M., Benagiano, G., and Guo, S.W. (2023). An Appraisal of the Tissue Injury and Repair (TIAR) Theory on the Pathogenesis of Endometriosis and Adenomyosis. 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