Skip to main content

Advertisement

Log in

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

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Matalliotakis IM, Katsikis IK, Panidis DK. Adenomyosis: what is the impact on fertility? Curr Opin Obstet Gynecol. 2005; 17(3): 261–264.

    PubMed  Google Scholar 

  2. 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.

    CAS  PubMed  Google Scholar 

  3. 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.

    CAS  PubMed  Google Scholar 

  4. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 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.

    PubMed  Google Scholar 

  6. 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.

    CAS  PubMed  Google Scholar 

  7. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 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.

    CAS  PubMed  Google Scholar 

  9. 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.

    CAS  PubMed  Google Scholar 

  10. 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.

    CAS  PubMed  Google Scholar 

  11. 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.

    CAS  PubMed  Google Scholar 

  12. 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.

    CAS  PubMed  Google Scholar 

  13. 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.

    CAS  PubMed  Google Scholar 

  14. Anaf V, Simon P, Fayt I, Noel J. Smooth muscles are frequent components of endometriotic lesions. Hum Reprod. 2000;15(4):767–771.

    CAS  PubMed  Google Scholar 

  15. Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;214(2):199–210.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 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.

    PubMed  PubMed Central  Google Scholar 

  17. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Richardson KC, Jarett L, Finke EH. Embedding in epoxy resins for ultrathin sectioning in electron microscopy. Stain Technol. 1960;35:313-323.

    CAS  PubMed  Google Scholar 

  20. 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.

    CAS  PubMed  Google Scholar 

  21. 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.

    Google Scholar 

  22. 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.

    PubMed  Google Scholar 

  23. 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.

    CAS  PubMed  Google Scholar 

  24. 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.

    CAS  PubMed  Google Scholar 

  25. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 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.

    CAS  PubMed  Google Scholar 

  27. Naftalin J, Jurkovic D. The endometrial-myometrial junction: a fresh look at a busy crossing. Ultrasound Obstet Gynecol. 2009;34(1):1–11.

    CAS  PubMed  Google Scholar 

  28. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 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.

    CAS  PubMed  Google Scholar 

  30. 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.

    CAS  Google Scholar 

  31. 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.

    Google Scholar 

  32. Komiyama S, Aoki D, Komiyama M, Nozawa S. Local activation of TGF-betal at endometriosis sites. J Reprod Med. 2007;52(4):306–312.

    CAS  PubMed  Google Scholar 

  33. 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.

    CAS  PubMed  Google Scholar 

  34. 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.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sylvia Mechsner MD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719116687855

Keywords

Navigation