Study on the common teratogenic pathway elicited by the fungicides triazole-derivatives.
Triazole-derivatives alter the pharyngeal apparatus morphogenesis of rodent embryos cultured in vitro. The hindbrain segmentation and the rhombencephalic neural crest cell (NCCs) migration are altered by Fluconazole exposure in vitro. The aim of the present work is to identify if a common pathogenic pathway is detectable also for other molecules of this class of compounds. 9.5 days post coitum (d.p.c.) old rat embryos were exposed in vitro to the teratogenic concentrations of Flusilazole, Triadimefon and Triadimenol and cultured for 24, 48 or 60 h. The expression and localisation of Hox-b1 and Krox-20 proteins (used as markers for hindbrain segmentation) were evaluated after 24 h of culture. The localisation and distribution of NCC was evaluated after 24, 30 and 48 h of culture. The morphology of the embryos was analysed after 48 h, while the branchial nerve structures were evaluated after 60 h of culture. Hindbrain segmentation and NCC migration alteration as well as pharyngeal arch and cranial nerve abnormalities were detected after exposure of the tested molecules. A common severe teratogenic intrinsic property for the tested molecules of this chemical class has been found, acting through alteration of the normal hindbrain developmental pattern.
Menegola
E
E
Department of Biology, University of Milan, via Celoria 26, 20133 Milan, Italy. elena.menegola@unimi.it
Broccia
M L
ML
Di Renzo
F
F
Massa
V
V
Giavini
E
E
D000818:Animals; D015415:Biomarkers; D003391:Cranial Nerves / Q000002:abnormalities / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D051767:Early Growth Response Protein 2; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D007150:Immunohistochemistry; D009421:Nervous System Malformations / Q000139:chemically induced* / Q000473:pathology; D009432:Neural Crest / Q000002:abnormalities / Q000473:pathology; D010614:Pharynx / Q000002:abnormalities; D011247:Pregnancy; D051381:Rats; D012249:Rhombencephalon / Q000002:abnormalities / Q000473:pathology; D013723:Teratogens / Q000633:toxicity*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014230:Triazoles / Q000633:toxicity*
D015415:Biomarkers; D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; C497328:Egr2 protein, rat; D005659:Fungicides, Industrial; D013723:Teratogens; D014157:Transcription Factors; D014230:Triazoles