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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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