Craniofacial and axial skeletal defects induced by the fungicide triadimefon in the mouse

Abstract

Triadimefon is teratogenic. The observed craniofacial malformations could be explained by an alteration of the rhombomeric organization and neural crest migration to the branchial arches; the axial abnormalities could be explained by the abnormal segmental identity specification.

Antifungal triazole derivative triadimefon induces ectopic maxillary cartilage by altering the morphogenesis of the first branchial arch

“…The treatment of mouse embryos with two triazole antifungals (triadimefon [FON] and fluconazole) during the early embryogenetic period, induced craniofacial (Menegola et al, 2005b;Tiboni and Giampietro, 2005) and axial abnormalities (Menegola et al, 2005b). Interestingly, maxillary ectopic cartilage, similar to that observed by Morriss-Kay (1993) after RA exposure, was detected after in vivo exposure of mouse embryos to FON (Menegola et al, 2005a). The present work studies the genesis of ectopic cartilage in rat embryos and fetuses exposed in vivo during the early embryogenetic period to the triazole derivative FON.…”

“…In particular, the in vitro exposure of postimplantation rat embryos to a number of triazole derivatives induces specific malformations at the branchial apparatus (fusion between the first and second branchial arch, hypoplasic branchial arch I or II), at the associated cranial nerves (V, VII, IX, X, fused, and disorganized), related to the incorrect migration of NCC streams from hindbrain to the branchial arches and to the abnormal segmentation of the rhombencephalic vesicle (Tiboni, 1993;Menegola et al, 2000Menegola et al, , 2001aMenegola et al, , 2003Menegola et al, , 2004Menegola et al, , 2005a. The treatment of mouse embryos with two triazole antifungals (triadimefon [FON] and fluconazole) during the early embryogenetic period, induced craniofacial (Menegola et al, 2005b;Tiboni and Giampietro, 2005) and axial abnormalities (Menegola et al, 2005b).…”

Grouping of histone deacetylase inhibitors and other toxicants disturbing neural crest migration by transcriptional profiling

“…Disturbance of such migration events can lead to severe malforma tions or diseases including Hirschsprung disease, Teratology of Fallot or DiGeorge syndrome in humans (Keyte and Hutson, 2012;Menendez et al, 2013). Impairment of NC development and function after exposure to a variety of chemicals, including pesticides, planar PCBs or anticonvulsant drugs has been observed in different vertebrate test systems (Di Renzo et al, 2007;Fuller et al, 2002;Grimes et al, 2008;Menegola et al, 2005a;Papis et al, 2006). Such animal based test systems are very limited in their throughput.…”

Biomarkers of teratogenesis: Suggestions from animal studies

“…Five case reports have been reported about infants exposed in utero to Fluconazole with a pattern of malformations resembling ABS [76]. Fluconazole, as other azole fungicides used in human therapy and in agriculture, is teratogenic in laboratory animals producing craniofacial and axial skeleton defects [77][78][79][80].…”