Enhanced expression of transforming growth factor-beta isoforms in the neural tube of embryos derived from diabetic mice exposed to cyclophosphamide.
We analyzed the expression pattern of transforming growth factor-beta isoforms (TGF-beta1, TGF-beta2 and TGF-beta3) in the developing brain of embryos derived from the normal and diabetic mice exposed to cyclophosphamide (CP), a cytotoxic teratogen. The CP-treated diabetic embryos showed significantly more TGF-beta1 and TGF-beta2 immunoreactive cells in the regions of telencephalon and diencephalon in comparison to that of CP-treated non-diabetic embryos. Moreover, no cells expressing TGF-beta isoforms were detectable in the developing brain of normal and diabetic embryos. The mRNA expression levels of TGF-beta isoforms were found to be significantly increased in the developing brain of CP-treated diabetic embryos compared to that of CP-treated non-diabetic embryos as measured by quantitative real time reverse transcription-polymerase chain reaction. The enhanced expression levels of TGF-beta isoforms appear to be associated with the increased frequency of neural tube defects observed in the diabetic embryos exposed to CP.
Lian
Qizhou
Q
Molecular Neurobiology Laboratory, Department of Anatomy, Faculty of Medicine, National University of Singapore, Singapore 117597, Singapore.
Samuel
Tay Sam Wah
TS
Dheen
S Thameem
ST
D000818:Animals; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism*; D003520:Cyclophosphamide / Q000633:toxicity*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013723:Teratogens / Q000633:toxicity*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3
D020033:Protein Isoforms; D013723:Teratogens; C508961:Tgfb1 protein, mouse; C509045:Tgfb3 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D003520:Cyclophosphamide