Myofibroblasts are evidence of chronic tissue microtrauma at the endometrial-myometrial junctional zone in uteri with adenomyosis
Abstract
Background Adenomyosis (AM) uteri exhibit hyperperistalsis. The latter causes a chronic tissue trauma at the endometrial-myometrial junctional zone (EMJZ). Upon tissue trauma, microdehiscences in the myometrium facilitate the translocation of basal endometrial fragments into the myometrium. There, a metaplasia (mediated by transforming growth factor β1 [TGFβ1] and connective tissue growth factor [CTGF]) occurs and AM lesions develop. The abundance of myofibroblasts in a tissue hallmarks metaplasia and points to a tissue microtrauma.Materials and methods To study if myofibroblasts-as an evidence of tissue microtrauma-are more abundant at EMJZ in AM-uteri, a case-control experimental study was carried out at Charité University Hospital-Endometriosis Research Centre. In all, 18 uteri with AM and 14 uteri without AM were obtained during laparoscopy-assisted vaginal hysterectomy. The immunolabeling of myofibroblastic metaplasia (alpha smooth muscle actin [ASMA] and collagen I), differentiated smooth muscle marker (desmin) and metaplasia mediators (TGF-β receptors 1, 2, 3 and CTGF) was investigated. The ultrastructure of myofibroblasts at EMJZ of AM uterus was characterized by transmission electron microscopy, in addition to an in vitro study to characterize myofibroblasts in the endometrium of non-AM uterus.Results Immunolabeling of ASMA and collagen I was significantly higher at EMJZ of AM uteri versus non-AM uteri. Furthermore, myofibroblasts were ultrastructurally characterized at EMJZ of AM. Endometrium of non-AM uterus exhibited 5% to 8% of its cells, expressing ASMA and collagen I. No difference was noted regarding metaplasia mediators immunolabeling between both the groups.Conclusion The abundant and persistent myofibroblasts (expressing ASMA/collagen I) at EMJZ in AM uteri are ultra-/microscopic evidence of chronic tissue trauma. They are of nonmyometrial origin, as they lack desmin immunolabeling.
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ERs and PRs are present not only in glands and stroma but also in the smooth muscle component of deep endometriosis, and the expression of a-smooth muscle actin and collagen I in and around endometriotic lesions support the notion of the metaplastic process.
“That E receptors (ERs) and PRs are present not only in glands and stroma but also in the smooth muscle component of deep endometriosis (229), and the expression of a-smooth muscle actin and collagen I in and around endometriotic lesions support the notion of the metaplastic process (230).”
From Pathogenesis of deep endometriosis (2017) · cites this paper as [230]
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Chang, S., Tsai, Y., Shieh, J., & Wu, W. (2024) · Journal of Cellular Physiology · doi:10.1002/jcp.31390
“…that TGF β induces fibroblasts to synthesize and contract ECM proteins and mediates fibroblast metaplasia into myofibroblasts, which is considered a master switch in the induction of the profibrotic program in uteri with adenomyosis and respiratory system (Ibrahim et al., 2017; Redington, 2000).”
Liu, T., Ma, S., & Si, X. (2025) · EXPLORE · doi:10.1016/j.explore.2025.103169
- Authors
- Ibrahim, M. G., Sillem, M., Plendl, J., Chiantera, V., Sehouli, J., & Mechsner, S.
- Affiliations
- Charité – Universitätsmedizin Berlin (DE)
- Freie Universität Berlin (DE)
- Corresponding author
- Mechsner, Sylvia
- Venue
- Reproductive Sciences
- Published
- 2017-10
- Volume
- 24
- Issue
- 10
- Pages
- 1410-1418
- ISSN
- 1933-7191 (ISSN-L)
- 1933-7205
- OpenAlex
- W2578931725
- Cited by
- 52
- References
- 35
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 8 · 2021: 8 · 2020: 5 · 2019: 5 · 2018: 9 · 2017: 3 · 2012: 1
- FWCI
- 6.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Reproductive Sciences (publishedVersion)
- PubMed (publishedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
- Funders
- FAZIT Stiftung
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Obstetrics and Gynecology › Uterine Myomas and Treatments
- Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
- Keywords
- adenomyosis, myofibroblasts, endometrial-myometrial junction, alpha-smooth muscle actin, type I collagen, desmin, TGF-beta, connective tissue growth factor
- MeSH terms
- Actins, Adult, Desmin, Endometrium, Female, Humans, Myometrium, Biomarkers, Case-Control Studies, Receptors, Transforming Growth Factor beta, Connective Tissue Growth Factor, Myofibroblasts, Adenomyosis
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