Ratlarda desidualizasyon süresince ekstrasellüler matriksin yeniden modellenmesinde laminin ve fibronektin ile reseptör altbirimleri integrin $beta$4 ve $alpha$5' in dağılımları ve muhtemel rolleri

Gebelik sürecine hazırlanan endometriyumdaki hücreler ve bunların ürünü olan stromal matriks elemanları, endometriyal kabullenmeye bağlı olarak, yapısal farklılaşmaya giderler. Endometriyal desidualizasyonla ortaya çıkan bu yapısal farklılaşmada, ‘ektrasellüler matriks (ESM) proteinlerinin ve adhezyon moleküllerinin rol almaları kaçınılmaz bir olgudur’ hipotezine bağlı olarak, ESM molekülleri laminin ve fibronektin ile adhezyon proteinleri integrin α5 ve β4’ün ortaya çıkış ve değişen dağılımlarının incelenmesi ile desidualizayon ve implantasyondaki rollerinin belirlenmesi amaçlandı. Bunun için ergin 40 adet gebe hayvandan, gebeliğin 4-8. günlerinde disseke edilmek üzere 5 deney grubu oluşturuldu. İmplantasyon alanlarından alınan 6-8 µm kalınlığındaki parafin doku seri kesitleri immunohistokimyasal teknikleri ile boyandı. Desidual reaksiyon alanı (DRA) ilk olarak gebeliğin 4. gününde görüldü. Gebeliğin 4 ve 5. gününde fibronektinin DRA’ının merkezinde ve 6-8. günlerde ise primer desidual reaksiyon alanında (PDRA) yoğunlaştığı gözlendi. İntegrin α5, 6. güne kadar fibronektine benzer bir boyanma göstermesine rağmen, bu günden sonra PDRA’da oldukça zayıftı. Lamininin başlangıçta lümen ve bez bazal laminalarında ve DRA’nın periferinde yoğun olarak boyanırken, 6. günden sonra lamininin sekonder desidual reaksiyon alanında (SDRA) yoğunlaştığı ve tüm gebelik günlerinde integrin β4’e paralel bir immunoreaktiviteye sahip olduğu gözlendi. Sonuç olarak, sıçan uterusu endometriyumunda desidual reaksiyonun gebeliğin 4-8. günleri arasında görüldüğünü ve sadece laminin ve fibronektin değil, aynı zamanda integrin α5 ve β4’ün de desidual doku yapılanmasına ve implantasyon olayına aktif olarak katıldıklarını söyleyebiliriz.

Distibutions and possible roles of laminin, fibronectin and their receptor subunits integrin $beta$4 and $alpha$5 in remodelling of extracellular matrix during decidualization in rats

In the endometrium preparing for pregnancy, the stromal matrix components of the cells and their products begin structural differentiation due to endometrial receptivity. According to the hypothesis that 'extracellular matrix (ECM) proteins and adhesion molecules take roles in the structural differentiation as a result of endometrial decidualization', our aim was to determine the roles of ECM molecules laminin, fibronectin and adhesion proteins integrin a5 and b4 in the decidulization and implantation by examining the emergence and changing distribution of these proteins. In this study, five experimental groups, consisting of 40 pregnant animals on pregnancy days 4-8, were used. Paraffin tissue serial sections that were 6-8 µm in thickness from the implantation areas were stained by immunohistochemical techniques. Decidual reaction area (DRA) was first observed on pregnancy day 4. Fibronectin was observed densely in the center of the DRA on pregnancy days 4, 5 and in the primary decidual area (PDRA) on pregnancy days 6-8. Although integrin a5 had a similar staining to fibronectin up to pregnancy day 6, it was very weak in PDRA after that day. While laminin was dense in the basal lamina of the lumen and glandular epithelium and in the periphery of the DRA at the beginning, it was observed to be dense in the secondary decidual area (SDRA) after pregnancy day 6 and to have paralel immunoreactivity to integrin b4 on all pregnancy days. In conclusion, we can say that decidual reaction appears on pregnancy days 4-8 and not only laminin and fibronectin but also integrin a5 and b4 take part actively in decidual tissue formation and implantation events in the endometrium of rat uterus.

___

  • 1. Abrahamsohn PA. Zorn MT. Implantation and Decidualization in Rodents. J. Exp. Zoo. 266: 603-628, 1993.
  • 2. Welsh AO, Enders AC. Occlusion and reformation of the rat uterine lumen during pregnancy. Am. J. Anat., 167: 463-477, 1983.
  • 3. Clark DE, Hurst RP, McLennan IS, Myers DB. Immunolocalization of collagen type I and laminin in the uterus on days 5 to 8 of embryo implantation in rat. Anat. Rec., 237: 8-20, 1993.
  • 4. Babiarz B, Romagnano L, Afonso S, Kurila G. Localization and expression fibronectin during mouse decidualization in vitro: Mechanisms of cell: matrix interactions. Dev. Dyn., 206: 330-342, 1996.
  • 5. Grinnell F, Head JR, Hoffpauir J. Fibronectin and cell shape in vivo: studies on the endometrium during pregnancy. J Cell Biol., 94: 597-606, 1982.
  • 6. Martello EM, Abrahamsohn PA. Collagen distribution in the mouse endometrium during decidualization. Acta. Anat., 127: 146-50, 1986.
  • 7. Albert E. The extracellular matrix in development. Organization of the early vertebrate embryo, Ed. By Nikolas Z., Plenum Press, New York, Chapter 4, 149-167, 1995.
  • 8. Mulholland J, Aplin JD, Ayad S, Hong L, Glasser SR. Loss of collagen type VI from rat endometrial stroma during decidualization. Biol. Reprod., 46: 1136-43, 1992.
  • 9. Zagris N, Stavridis V. The expression of the genes for laminin in the early embryo. Organization of the early vertebrate embryo, Ed. Zagris N., Plenum Press New York, 169-183, 1995.
  • 10. Yamada K M. Fibronectin and other cell interactive glycoproteins. Cell biology of extracellular matrix. Second edition, Ed. Elizabeth D. Hay, Plenum Press. New York, Chapter 4, 111-46, 1991.
  • 11. Darnel J. Molecular Cell Biology, 3rd edition; Scientific American Books, Oxford, Chapter 24, 1124-97, 1995.
  • 12. Mueller S C, Chen W T. Cellular invasion into matrix beads: Localization of β1 integrins and fibronectin to the invadopodia. J. of Cell Science, 99: 213-226, 1991.
  • 13. Bischof P, Martelli M, Campana A. The regulation of endometrial and trophoblastic metalloproteinases during blastocyst implantation Contracept. Fertil. Sex., 22: 48-52, 1994.
  • 14. Blankenship T N, Given R L. Penetration of the uterine epithelial basement membrane during blastocyst implantation in the mouse. Anat. Rec., 231: 196-204, 1992.
  • 15. Bischof P, Redard M, Gindre P, Vassilakos P, Campana A. Localization of alpha 2, alpha 5 and alpha 6 integrin subunits in human endometrium, decidua and trophoblast. Eur. J. Obstct. Gynecol. Reprod. Biol., 29; 51: 217- 226, 1993.
  • 16. Nishida T, Murakami J, Otori T. Expression of fibronectin receptor (integrin) in the uterus of rats in relation to the estrous cycle. Histochemistry, 96: 279-83, 1991.
  • 17. Fazleabas AT, Bell SC, Fleming S. Sun J, Lessey BA. Distribution of integrins and the extracellular matrix proteins in the baboon endometrium during menstrual cycle and early pregnancy. Biol. Reprod., 56: 348-56, 1997.
  • 18. Albers A, Thie M, Hohn HP, Denker HW. Differential expression and localization of integrins and CD44 in the membrane domains of human uterine epithelial cells during menstrual cycle. Acta Anat., 153: 12-19, 1995.
  • 19. Glasser SR, Lampelo S, Munir MI, Julian J. Expression of desmin, laminin and fibronectin during in situ differentiation (decidualization) of rat uterine stromal cells. Differentiation, 35: 132-142, 1987.
  • 20. Hsu SM, Raine L, Fanger H. Use of avidin-biotin peroxidase complex (ABC) in immunoperoxidase techniques. A comparison between ABC and unlabelled antibody (PAP) procedures. J. Histochem Cytochem., 29: 577-580, 1981.
  • 21. Kramer B. Changes in vascular permeability and desiduoma formation during the peri-implantation period of the rat in response to exogenous gonadotropins. Anat. Rec., 242: 20-24, 1997.
  • 22. Demir R, Üstünel İ, Demir N. Light and electron microscopical observations on cellular interactions during initial stages of implantation and trophoblastic invasion in rats. Placenta, 10: 464-465, 1989.
  • 23. Demir R. Functional differentiation of the blastocystic ring trophoblast cells in the rat. Biomedical Reviews, 8: 127- 132, 1997.
  • 24. Blankenship TN, Given RL. Loss of laminin and type 4 collagen in uterine luminal epithelial basement membranes during blastocyst implantation in the mouse. Anat. Rec., 243: 27-36, 1995.
  • 25. Zorn TM, Bevilacqua EM, Abrahamsohn PA. Collagen remodelling during decidualization in the mouse. Cell Tissue Res., 244: 443-48, 1986.
  • 26. Aplin JD. The cell biology of human implantation. Placenta, 17; 269-75, 1996.
  • 27. Rider V, Carlone DL, Witrock D, Oliver N. Uterine Fibronectin mRNA content and localization are modulated during implantation. Dev. Dyn., 195: 1-14, 1992.
  • 28. Damsky CH, Fitzgerald ML, Fisher JS. Distribution patterns of extracellular matrix component and adhesion receptors are intricately modulated during first trimester cytotrophoblast differentiation along the invasive pathway, in vivo. J. Clin. Invest., 89: 210-22, 1992.
  • 29. Damsky CH, Librach C, Lim KH, Fitzgerald ML, Logan SK, Fisher SJ. Integrin switching regulates normal trophoblast invasion. Development, 120: 3657-3666, 1994.
  • 30. Tominaga T. Studies on the mechanism of embryo implantation. Nippon Sanka Fujinka Gakkai Zasshi, 48: 591- 603, 1996.
  • 31. Lessey BA, Castelbaum AJ, Buck CA, Lei Y, Yowell CW, Sun J. Further characterization of endometrial integrins during the menstrual cycle and in pregnancy. Fertil. Steril., 6: 497-506, 1994.
  • 32. Gumbiner BM. Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell, 84: 345-357, 1996.
  • 33. Sueka K, Schiokawa S, Miyazaki T, Kuji N, Tanaka M, Yosimura Y. Integrins and reproductive physiology: expression and modulation in fertilization, embryogenesis and implantation. Fertil. Steril., 67: 799-811, 1997.
  • 34. Yoshimura Y. Integrins: expression, modulation and signaling in fertilization, embryogenesis and implantation. Keio J. Med., 46: 16-24, 1997.
Turkish Journal of Biology-Cover
  • ISSN: 1300-0152
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK