Molecular aspects of azoles-induced teratogenesis

IMPORTANCE OF THE FIELD: Antifungal azole compounds are widely used as antimycotics in plant, veterinary and human therapies. Their pharmacological action is based on the inhibition of the CYP450 enzyme catalyzing the synthesis of steroids required for the synthesis and integrity of fungal cell wall. Azoles are teratogenic in animal models and are under investigation for potential human developmental toxic effects. Rational approaches to prevent teratogenic effects require knowledge of the underlying mechanisms. AREAS COVERED IN THIS REVIEW: This review highlights the current knowledge on the molecular mechanisms that are potentially involved in the teratogenic response to azoles. WHAT THE READER WILL GAIN: A comprehensive review of the literature on this subject including experimental and clinical studies. Particular attention is focused on the mechanistic role played by CYP26 family inhibition. TAKE HOME MESSAGE: Significant advancements have been made in the comprehension of molecular mechanisms underlying teratogenic effects mediated by azole derivatives. Increasing evidence is linking disruption of embryonic retinoic acid homeostasis as a crucial determinant of azole-mediated teratogenesis.