Diabetes teratogenicity in mice is accompanied with distorted expression of TGF-β2 in the uterus

A. Fein, N. Magid, S. Savion, H. Orenstein, J. Shepshelovich, A. Ornoy, A. Torchinsky, V. Toder

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים

19 ציטוטים ‏(Scopus)

תקציר

Early embryonic deaths as well as malformed newborns are among complications of the diabetic pregnancy. Cytokines and growth factors operating in the embryonic vicinity are found to be among factors that determine the sensitivity of embryos to external and internal detrimental stimuli, including diabetes. Transforming Growth Factor-β2 (TGF-β2) has been shown to be essential for embryonic development and survival. In the present work, we evaluated the pattern of TGF-β2 expression in the uterus of streptozotocin-induced diabetic mice, demonstrating a decreased reproductive performance and elevated percentage of litters with severely malformed fetuses. Since stimulation of the maternal immune system was found to increase the resistance of mouse embryos to the teratogenic effect of diabetes, the effect of immunopotentiation on the expression of the cytokine was also investigated. TGF-β2 expression was studied at the mRNA level by using the in situ hybridization technique and at the protein level by using the immunohistochemical analysis. A clear decrease in TGF-β2 mRNA expression in the uterus of diabetic mice was observed at examined time points: days 1, 5, and 9 of pregnancy. Also, an evident reduction in TGF-β2, the protein expression in the uterus of diabetic mice, was demonstrated at these time points. Maternal immunopotentiation that improved the reproductive performance of diabetic mice and reduced the number of the litters with malformed fetuses was also accompanied by a clear increase in the level of TGF-β2 mRNA expression in the pregnant uteri. The above results clearly demonstrate that the embryotoxic effect of diabetes is accompanied by an alteration of TGF-β2 expression. Immunopotentiation that was shown to improve the reproductive performance of the diabetic mice was accompanied by a partial normalization of TGF-β2 expression in embryonic vicinity.

שפה מקוריתאנגלית
עמודים (מ-עד)59-71
מספר עמודים13
כתב עתTeratogenesis Carcinogenesis and Mutagenesis
כרך22
מספר גיליון1
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - 2002
פורסם באופן חיצוניכן

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