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RETİNOİK ASİT UYGULANAN SIÇANLARIN PLASENTALARINDA MMP-2 VE MMP-13 İMÜNREAKTİVİTESİNİN İNCELENMESİ

INVESTIGATION OF MMP-2 AND MMP-13 IMMUNOREACTIVITY IN PLACENTA OF RATS TREATED WITH RETINOIC ACID

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Abstract (2. Language): 
Objective: Matrix metalloproteinases (MMPs) are enzymes and play important roles at implantation by degradation of extracellular matrix. Retinoic acid (RA) is an important molecule has effects on MMP synthesis, embriyonic development and trophoblast invasion at placentation. In this study we investigated the MMP-2 and MMP-13 immunoreactivity on rat placenta treated by RA. Materials and Methods: In this study 16 female Spraque Dawley rats were used, divided equally for control (8) and RA (8) treated groups. Rats were treated by 13-cis RA (40mg/kg/day) by gavaj for 3 days. For immunochemical study we used rabbit polyclonal MMP-13 and mouse monoclonal MMP-2 antibody. Results: In the control group the trophoblast giant cells show ed strong (+++) and chorioamniotic membrane moderate (++) positivity for MMP-2. There was no MMP-2 immunoreactivity detected at trophoblastic giant cells of RA treated group in contrast to the strong positivity were detected at chorion epithelium. Moderate MMP-13 immunoreactivity was detected at trophoblastic giant cells and chorioamniotic membrane of control group. In RA treated group trophoblastic giant cells showed moderate, chorioamniotic membrane showed strong reactivity for MMP-13. Conclusion: It is convinced that exogenously applied retinoic acid affects implantation negatively by repressing MMP-2 synthesis in trophoblastic giant cells and decidua, impair membrane stabilization by increasing MMP-2 and MMP-13 synthesis in chorioamniotic membrane and therefore prevent survival.
Abstract (Original Language): 
Amaç: Matriks metalloproteinazlar (MMP) hücrelerarası matriks yıkımında rol alarak implantasyonun gerçekleĢmesine yardımcı olan enzimlerdir. Retinoik asit (RA); MMP üretimi üzerine etkisi olduğu düĢünülen, trofoblast invazyonunda rolü olan bir moleküldür. ÇalıĢmamızda retinoik asit uygulanan gebe sıçanların plasentalarında MMP-2 ve MMP-13 immünreaktivitesinin incelenmesi amaçlandı. Gereç ve Yöntem: ÇalıĢmada kontrol (8 adet) ve deney (8 adet) gruplarında toplam 16 adet diĢi Spraque Dawley türü sıçan kullanıldı. Sıçanlar gebe bırakılarak deney grubundakilere gastrulasyon döneminde 3 gün süre ile 40mg/kg/gün 13-cis retinoik asit oral yolla uygulandı. Gebeliğin orta döneminde (10-14 gün) plasentalardan alınan kesitler immünhistokimyasal olarak Streptavidin- Biyotin yöntemi kullanılarak rabbit poliklonal MMP-13 antikoru ve mouse monoklonal MMP-2 antikoru ile iĢaretlendi. Bulgular: Kontrol grubuna ait plasentalarda MMP-2 immünreaktivitesi trofoblastik dev hücrelerde kuvvetli pozitif (+++), koriyo-amniyotik zarda ise orta derecede pozitif (++) bulundu. RA uygulanan grupta trofoblastik dev hücrelerde MMP-2 immünreaktivitesi saptanmadı, buna karĢın koriyo-amniotik zarda kuvvetli pozitiflik mevcuttu. MMP-13 immünreaktivitesi ise kontrol grubu dev hücrelerinde ve korio-amniyotik zarda orta derecede (++) pozitifti. RA grubunda dev hücrelerde değiĢiklik görülmezken koriyo-amniyotik zarda kuvvetli pozitif (+++) iĢaretlenme mevcuttu. Sonuç: Eksojen olarak uygulanan retinoik asitin trofoblastik dev hücrelerde ve desiduada MMP-2 sentezini baskılayarak implantasyonu olumsuz etkileyebileceği ve koriyo-amniyotik zarda ise MMP-2 ve MMP-13‟ü arttırmak suretiyle membran stabilizasyonunu bozabileceği, bunlara bağlı olarak hayatta kalımı engelleyebileceği kanaatine varıldı.
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REFERENCES

References: 

1- Alexander CM, Hansell EJ, Behrendtsen O, Flannery ML, Kishnani N, Hawkes SP, Werb Z. Expression and function of matriks metalloproteinases and their inhibitors at the maternal-embryonic boundary during mouse embryo implantation. Development 1996; 122: 1723-1736.
2- Braunhut SJ, Moses MA. Retinoids modulate endothelial cell production of matrix-degrading proteases and tissue inhibitors of metalloproteinases (TIMP). The Journal of Biological Chemistry 1994; 269 : 13472-13479.
3- Das SK, Yano S, Wang J, Edwards DR, Nagase H, Dey SK. Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in the Mouse Uterus During the Peri-Implantation Period. Developmental Genetics 1997; 21:44-54.
4- El-Hashash AH, Esbrit P, Kimber SJ. PTHrP promotes murine secondary trophoblast giant cell differentiation through induction of endocycle, upregulation of giant-cell-promoting transcription factors and suppression of other trophoblast cell types. Differentiation 2005; 73: 154–174.
5- Fortunato SJ, Menon R. Screening of Novel Matrix Metalloproteinases (MMPs) in Human Fetal Membranes. Journal of Assisted Reproduction and Genetics 2002; 19:483-486.
6- Goldman S, Weiss A, Eyali V, Shalev E. Differential activity of gelatinases (matrix metalloproteinases 2 and 9) in the fetal membranes and decidua, associated with labour. Molecular Human Reproduction 2003; 9: 367-373.
7- Hasan S, Nakajima M. Retinoic acid synergizes with cyclic AMP to enhance MMP-2 basal promoter activity. Biochemical and Biophysical Research Communications 1999; 258: 663-667.
8- Hendrix MJC, Wood WR, Seftor EA, Lotan D, Nakajima M, Misiorowski RL, SeftorREB, Stetler-Stevenson WG, Bevacqua SJ, Liotta LA, Sobel ME, Lotan R. Retinoic acid inhibition of human melanoma cell invasion through a reconstituted basement membrane and its relation to decreases in the expression of proteolytic enzymes and motility factor receptor. Cancer Res 1990; 50:4121-4130.
9- Huang F. Effects of retinoic acid on morula-stage embryo development in mice. Chang Gung Med J 2008;31:44-51.
10- Kanai-Azuma M, Kanai Y, Matsuda H, Kurohmaru M, Tachi C, Yazaki K, Hayashi Y. Nerve growth factor
50
23- Teesalu T, Masson R, Basset P, Blasi F, Talarıco D. Expression of matriks metalloproteinases during murine chorioallantoic placenta maturation. Developmental Dynamics 1999; 214: 248-258.
24- Tremblay GB, Kunath T, Bergeron D, Lapointe L, Champigny C, Bader JA, Rossant J, Giguere V. Diethylstilbestrol regulates trophoblast stem cell differentiation as a ligand of orphan nuclear receptor ERR beta. Genes Dev 2001; 15: 833–838.
25- Uchide K, Ueno H, Inoue M, Sakaı A, Fujimoto N, Okada Y. Matrix metalloproteinase-9 and tensile strength of fetal membranes in uncomplicated labor. Obstet Gynecol 2000; 95: 851-855.
26- Ulug U, Goldman S, Ben-Shlomo I, Shalev E. Matrix metalloproteinase (MMP)- 2 and MMP-9 and their inhibitor, TIMP-1, in human term decidua and fetal membranes: the effect of prostaglandin F2α and indomethacin. Molecular Human Reproduction 2001; 7: 1187-1193.
27- Walter I, Schönkypl S. Extracellular matrix components and matrix degrading enzymes in the feline placenta during gestation. Placenta 2006; 27: 291-306.
28- Weiss A, Goldman S, Shlomo IB, Eyali V, Leibovitz S, Shalev E. Mechanisms of matrix metalloproteinase-9 and matrix metalloproteinase-2 inhibition by N-acetylcysteine in the human term decidua and fetal membranes. Am J Obstet Gynecol 2003; 189:1758-1763.
29- Winterhager E, Reuss B, Hellmann P, Spray DC, Gruemmer R. Gap junctionand tissue invasion: A comparison of tumorigenesis and pregnancy. Clin. Exp. Pharmacol. Physiol 1996; 23: 1058-1061.
30- Xu P, Alfaidy N, Challis JRG. Expression of matriks metalloproteinase (MMP)-2 and MMP-9 in human placenta and fetal membranes in relation to preterm and term labor. The Journal of Clinical Endocrinology & Metabolism 2002; 87: 1353-1361.
31- Xu P, Wang Y, Zhu S, Luo S, Piao Y, Zhuang K. Expression of matrix metalloproteinase-2, -9, and -14, Tissue Inhibitors of metalloproteinase-1, and Matrix proteins in human placenta during the first trimester. Biology of Reproduction 2000; 62: 988-994.
32- Yan J, Tanaka S, Oda M, Makino T, Ohgane J, Shiota K. Retinoic acid promotes differentiation of trophoblast stem cells to a giant cell fate. Developmental Biology 2001; 235: 422-432.
promotes giant-cell transformation of mouse trophoblast cells in vitro. Biochem. Biophys. Res. Commun 1997; 231: 309–315.
11- Maden M. Retinoic acid in development and rejeneration. J. Biosci. 1996; 21: 299-312.
12- Morriss-Kay GM, Murphy P, Hill RE, Davidson DR. Effects of retinoic acid excess on expression of Hox-2.9 and Krox-20 and on morphological segmentation in the hindbrain of mouse embryos. EMBO J 1991;10:2985-95.
13- Mott JD, Werb Z. Regulation of matrix biology by matrix metalloproteinases. Current Opinion in Cell Biology 2004; 16:558-564.
14- Nadra K, Anghel S, Joye E, Tan NS, Basu-Modak S, Trono D, Wahli W, Desvergne B. Differentiation of trophoblast giant cells and their metabolic functions are dependent on peroxisome proliferator – activated receptor β/δ. Molecular and Cellular Biology 2006; 26: 3266-3281.
15- Nakajima M, Lotan D, Baig M, Carralero LM, Wood WR, Hendrix MJC, Lotan R. Inhibition by retinoic acid of type IV collagenolysis and invasion through reconstituted basement membrane by metastatic rat mammary adenocarcinoma cells. Cancer Res 1989;49: 1698-1706.
16- Niu R, Okamoto T, Iwase K, Nomura S, Mizutani S. Quantitative analysis of matrix metalloproteinases -2 and -9, and their tissue inhibitors-1 and -2 in human placenta throughout gestation. Life Sciences 2000; 66: 1127-1137.
17- Ota A, Yonemoto H, Someya A, Itoh S, Kinoshita K, Nagaoka I. Changes in matrix metalloproteinase 2 activities in amniochorions during premature rupture of membranes. Journal of the Society for Gynecologic Investigation 2006; 13:592-597.
18- Sapin V, Begue R, Dastugue B, Chambon P, Dolle P. Retinoids and Mouse placentation. Trophoblast Research 1998; 12:57-76.
19- Seval Y, Akkoyunlu G, Demir R, Asar M. Distribution patterns of matrix metalloproteinase (MMP)-2 and -9 and their inhibitors (TIMP-1 and TIMP-2) in the human decidua during early pregnancy. Acta Histochemica 2004; 106: 353-362.
20- Simmons DG, Fortier AL, Cross JC. Diverse subtypes and developmental origins of trophoblast giant cells in the Mouse placenta. Developmental Biology 2007; 304:567-578.
21- Staun-Ram E, Goldman S, Gabarin D, Shalev E. Expression and importance of matrix metalloproteinase 2 and 9 (MMP-2 and -9) in human trophoblast invasion. Reproductive Biology and Endocrinology 2004; 2:59.
22- Stephanou A, Handwerger S. Retinoic acid and thyroid hormone regulate placental lactogen expression in human trophoblast cells. Endocrinology 1995; 136:933-938.23- Teesalu T, Masson R, Basset P, Blasi F, Talarıco D. Expression of matriks metalloproteinases during murine chorioallantoic placenta maturation. Developmental Dynamics 1999; 214: 248-258.
24- Tremblay GB, Kunath T, Bergeron D, Lapointe L, Champigny C, Bader JA, Rossant J, Giguere V. Diethylstilbestrol regulates trophoblast stem cell differentiation as a ligand of orphan nuclear receptor ERR beta. Genes Dev 2001; 15: 833–838.
25- Uchide K, Ueno H, Inoue M, Sakaı A, Fujimoto N, Okada Y. Matrix metalloproteinase-9 and tensile strength of fetal membranes in uncomplicated labor. Obstet Gynecol 2000; 95: 851-855.
26- Ulug U, Goldman S, Ben-Shlomo I, Shalev E. Matrix metalloproteinase (MMP)- 2 and MMP-9 and their inhibitor, TIMP-1, in human term decidua and fetal membranes: the effect of prostaglandin F2α and indomethacin. Molecular Human Reproduction 2001; 7: 1187-1193.
27- Walter I, Schönkypl S. Extracellular matrix components and matrix degrading enzymes in the feline placenta during gestation. Placenta 2006; 27: 291-306.
28- Weiss A, Goldman S, Shlomo IB, Eyali V, Leibovitz S, Shalev E. Mechanisms of matrix metalloproteinase-9 and matrix metalloproteinase-2 inhibition by N-acetylcysteine in the human term decidua and fetal membranes. Am J Obstet Gynecol 2003; 189:1758-1763.
29- Winterhager E, Reuss B, Hellmann P, Spray DC, Gruemmer R. Gap junctionand tissue invasion: A comparison of tumorigenesis and pregnancy. Clin. Exp. Pharmacol. Physiol 1996; 23: 1058-1061.
30- Xu P, Alfaidy N, Challis JRG. Expression of matriks metalloproteinase (MMP)-2 and MMP-9 in human placenta and fetal membranes in relation to preterm and term labor. The Journal of Clinical Endocrinology & Metabolism 2002; 87: 1353-1361.
31- Xu P, Wang Y, Zhu S, Luo S, Piao Y, Zhuang K. Expression of matrix metalloproteinase-2, -9, and -14, Tissue Inhibitors of metalloproteinase-1, and Matrix proteins in human placenta during the first trimester. Biology of Reproduction 2000; 62: 988-994.
32- Yan J, Tanaka S, Oda M, Makino T, Ohgane J, Shiota K. Retinoic acid promotes differentiation of trophoblast stem cells to a giant cell fate. Developmental Biology 2001; 235: 422-432.

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