Myofibroblasts Are Evidence of Chronic Tissue Microtrauma at the Endometrial-Myometrial Junctional Zone in Uteri With Adenomyosis

Mohamed Gamal Ibrahim, Martin Sillem, Johanna Plendl, Vito Chiantera, Vito Chiàntera, Jalid Sehouli, Sylvia Mechsner
Reproductive sciences (Thousand Oaks, Calif.) · 2017 · vol. 24(10) , pp. 1410–1418 · doi:10.1177/1933719116687855 · PMID:28093048 · W2578931725
article OA: closed CC0 ⤵ 39 in-corpus citations
Full text JSON View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06+body, 2026-06-06 ⓘ

This study found significantly higher levels of ASMA and collagen I at the endometrial-myometrial junctional zone in uteri with adenomyosis compared to those without.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-06, 2026-06-06 · read from full text ⓘ

This case-control study examined whether myofibroblasts, as markers of tissue microtrauma, are more abundant at the endometrial–myometrial junctional zone (EMJZ) in uteri with adenomyosis. Uterine tissue from 18 adenomyosis uteri and 14 non-adenomyosis uteri obtained during laparoscopy-assisted vaginal hysterectomy was analyzed using immunolabeling for alpha smooth muscle actin (ASMA) and collagen I, smooth muscle differentiation (desmin), and mediators (TGF-β receptor 1–3 and CTGF), with transmission electron microscopy and an in vitro component to characterize myofibroblasts in non-adenomyosis endometrium. ASMA/collagen I immunolabeling was significantly higher at the EMJZ in adenomyosis, and ultrastructural myofibroblasts were identified there, while no difference was observed in labeling of metaplasia mediators between groups; the authors also report that these myofibroblasts were desmin-negative, supporting nonmyometrial origin. This paper is centrally about endometriosis and/or adenomyosis — it directly investigates adenomyosis-related chronic tissue microtrauma with myofibroblasts at the EMJZ.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Full text 8,755 characters · extracted from oa-doi-fallback · 5 sections · click to expand

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 (βI [TGFβI] 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 Charite 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. Similar content being viewed by others

References

Matalliotakis IM, Katsikis IK, Panidis DK. Adenomyosis: what is the impact on fertility? Curr Opin Obstet Gynecol. 2005; 17(3): 261–264. Kunz G, Beil D, Huppert P, Noe M, Kissler S, Leyendecker G. Adenomyosis in endometriosis-prevalence and impact on fertility. Evidence from magnetic resonance imaging. Hum Reprod. 2005;20(8):2309–2316. Streuli I, Dubuisson J, Santulli P, de Ziegler D, Batteux F, Chapron C. An update on the pharmacological management of adenomyosis. Expert Opin Pharmacother. 2014;15(16):2347–2360. Taran FA, Stewart EA, Brucker S. Adenomyosis: epidemiology, risk factors, clinical phenotype and surgical and interventional alternatives to hysterectomy. Geburtshilfe Frauenheilkd. 2013;73(9):924–931. Kunz G, Leyendecker G. Uterine peristaltic activity during the menstrual cycle: characterization, regulation, function and dys-function. Reprod Biomed Online. 2002;4(suppl 3):5–9. Uduwela AS, Perera MA, Aiqing L, Fraser IS. Endometrial-myometrial interface: relationship to adenomyosis and changes in pregnancy. Obstet Gynecol Surv. 2000;55(6):390–400. Leyendecker G, Wildt L, Mall G. The pathophysiology of endo-metriosis and adenomyosis: tissue injury and repair. Arch Gynecol Obstet. 2009;280(4):529–538. Mechsner S, Bartley J, Loddenkemper C, Salomon DS, Starzinski-Powitz A, Ebert AD. Oxytocin receptor expression in smooth muscle cells of peritoneal endometriotic lesions and ovarian endometriotic cysts. Fertil Steril. 2005;83(suppl 1): 1220–1231. Mechsner S, Grum B, Gericke C, Loddenkemper C, Dudenhausen JW, Ebert AD. Possible roles of oxytocin receptor and vasopressinlalpha receptor in the pathomechanism of dysperistalsis and dysmenorrhea in patients with adenomyosis uteri. Fertil Steril. 2010;94(7):2541–2546. Ibrahim MG, Chiantera V, Frangini S, et al. Ultramicrotrauma in the endometrial-myometrial junctional zone and pale cell migration in adenomyosis. Fertil Steril. 2015;104(6):1475–1483. e1471-1473. Chen YJ, Li HY, Huang CH, et al. Oestrogen-induced epithelial-mesenchymal transition of endometrial epithelial cells contributes to the development of adenomyosis. J Pathol. 2010;222(3):261–270. Daimon E, Shibukawa Y, Wada Y. Calponin 3 regulates stress fiber formation in dermal fibroblasts during wound healing. Arch Dermatol Res. 2013;305(7):571–584. Leyendecker G, Wildt L. A new concept of endometriosis and adenomyosis: tissue injury and repair (TIAR). Horm Mol Biol Clin Investig. 2011;5(2):125–142. Anaf V, Simon P, Fayt I, Noel J. Smooth muscles are frequent components of endometriotic lesions. Hum Reprod. 2000;15(4):767–771. Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;214(2):199–210. Lipson KE, Wong C, Teng Y, Spong S. CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis. Fibrogenesis Tissue Repair. 2012;5(suppl 1):S24. Maybin JA, Barcroft J, Thiruchelvam U, Hirani N, Jabbour HN, Critchley HO. The presence and regulation of connective tissue growth factor in the human endometrium. Hum Reprod. 2012;27(4):1112–1121. Goldhirsch A, Winer EP, Coates AS, et al; Panel members. Personalizing the treatment of women with early breast cancer: high-lights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol. 2013;24(9):2206–2223. Richardson KC, Jarett L, Finke EH. Embedding in epoxy resins for ultrathin sectioning in electron microscopy. Stain Technol. 1960;35:313-323. Stomper PC, Davis SP, Sonnenfeld MR, Meyer JE, Greenes RA, Eberlein TJ. Efficacy of specimen radiography of clinically occult noncalcified breast lesions. AJR Am J Roentgenol. 1988;151(1):43–47. Kissler S, Zangos S, Wiegratz I, et al. Utero-tubal sperm transport and its impairment in endometriosis and adenomyosis. Ann N Y AcadSci. 2007;1101:38-48. Hagiwara H, Ohwada N, Aoki T, Suzuki T, Takata K. Immuno-histochemical and electron microscopic observations of stromal cells in the human oviduct mucosa. Med Mol Morphol. 2008;41(4):221–226. Nasu K, Nishida M, Matsumoto H, et al. Regulation of proliferation, motility, and contractivity of cultured human endometrial stromal cells by transforming growth factor-beta isoforms. Fertil Steril. 2005;84(suppl 2):1114–1123. Oliver C, Montes MJ, Galindo JA, Ruiz C, Olivares EG. Human decidual stromal cells express alpha-smooth muscle actin and show ultrastructural similarities with myofibroblasts. Hum Reprod. 1999;14(6):1599–1605. Strakova Z, Livak M, Krezalek M, Ihnatovych I. Multipotent properties of myofibroblast cells derived from human placenta. Cell Tissue Res. 2008;332(3):479–488. Grinnell F, Zhu M, Carlson MA, Abrams JM. Release of mechanical tension triggers apoptosis of human fibroblasts in a model of regressing granulation tissue. Exp Cell Res. 1999;248(2):608–619. Naftalin J, Jurkovic D. The endometrial-myometrial junction: a fresh look at a busy crossing. Ultrasound Obstet Gynecol. 2009;34(1):1–11. Hinz B, Gabbiani G, Chaponnier C. The NH2-terminal peptide of alpha-smooth muscle actin inhibits force generation by the myofibroblast in vitro and in vivo. J Cell Biol. 2002;157(4):657–663. Green AR, Styles JA, Parrott EL, et al. Neonatal tamoxifen treatment of mice leads to adenomyosis but not uterine cancer. Exp Toxicol Pathol. 2005;56(4–5):255–263. Shoae-Hassani A, Sharif S, Seifalian AM, Mortazavi-Tabatabaei SA, Rezaie S, Verdi J. Endometrial stem cell differentiation into smooth muscle cell: a novel approach for bladder tissue engineering in women. BJUInt. 2013;112(6):854–863. Shen N, Li X, Zhou T, et al. Shensong Yangxin Capsule prevents diabetic myocardial fibrosis by inhibiting TGF-betal/Smad sig-naling. JEthnopharmacol. 2014;157:161-170. Komiyama S, Aoki D, Komiyama M, Nozawa S. Local activation of TGF-betal at endometriosis sites. J Reprod Med. 2007;52(4):306–312. Inagaki N, Ung L, Otani T, Wilkinson D, Lopata A. Uterine cavity matrix metalloproteinases and cytokines in patients with leio-myoma, adenomyosis or endometrial polyp. Eur J Obstet Gynecol Reprod Biol. 2003; 111 (2): 197–203. Di Lieto A, Pollio F, De Falco M, et al. Collagen content and growth factor immunoexpression in uterine lower segment of type IA osteogenesis imperfecta: relationship with recurrent uterine rupture in pregnancy. Am J Obstet Gynecol. 2003;189(2):594–600. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Ibrahim, M.G., Sillem, M., Plendl, J. et al. Myofibroblasts Are Evidence of Chronic Tissue Microtrauma at the Endometrial-Myometrial Junctional Zone in Uteri With Adenomyosis. Reprod. Sci. 24, 1410–1418 (2017). https://doi.org/10.1177/1933719116687855 Published: Issue date: DOI: https://doi.org/10.1177/1933719116687855

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

⚙ Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback ⓘ

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

adenomyosis

MeSH descriptors

Adenomyosis Endometrium Myofibroblasts Myometrium Actins Actins Adenomyosis Adenomyosis Adult Biomarkers Biomarkers Case-Control Studies Connective Tissue Growth Factor Connective Tissue Growth Factor Desmin Desmin Endometrium Endometrium Female Humans

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (35)

Cited by (39)

Source provenance

europepmc
last seen: 2026-06-04T01:30:01.192114+00:00
openalex
last seen: 2026-06-04T00:00:01.174412+00:00
pubmed
last seen: 2026-05-13T22:20:37.704673+00:00
unpaywall
last seen: 2026-06-02T02:00:03.124865+00:00
License: CC0 · commercial use OK