Related Experiment Video
Updated: Jun 23, 2026
Assessing Teratogenic Changes in a Zebrafish Model of Fetal Alcohol Exposure
Published on: March 20, 2012
Fluconazole alters CYP26 gene expression in mouse embryos
Gian Mario Tiboni1, Francesca Marotta, Erminia Carletti
1Sezione di Ostetricia e Ginecologia, Dipartimento di Medicina e Scienze dell'Invecchiamento, Facoltà di Medicina e Chirurgia, Università G. d'Annunzio di Chieti-Pescara, Italy. tiboni@unich.it
Abstract:
Disruption of embryonal retinoic acid homeostasis has been postulated to represent an etiological factor involved in the onset of fluconazole-induced teratogenesis. In the present study the impact of a teratogenic pulse of fluconazole on the gene expression of cytochrome P450 (CYP) 26 isoforms, which plays a central role in maintaining proper retinoic acid levels by mediating its degradation, was investigated. ICR pregnant mice were orally administered with 0 (vehicle) or 700mg/kg of fluconazole on gestation day 8. Embryos were collected 12, 24 and 48h after treatment. Quantitative real-time reverse-transcription polymerase chain reaction (quantitative real-time RT-PCR) assay was used to quantify the mRNA expression of CYP26a1, CYP26b1 and CYP26c1 in embryos. As result, fluconazole exposure was associated to an up-regulation of CYP26a1, CYP26b1, whereas no significant change was identified for the CYP26c1 isoform. This study demonstrates the capacity of fluconazole to alter CYP26 gene expression in mouse embryos.
Insights
Fluconazole exposure during pregnancy can disrupt retinoic acid balance, potentially causing birth defects. This study found fluconazole increases the expression of key genes (CYP26a1, CYP26b1) involved in retinoic acid metabolism in mouse embryos.
Area of Science:
- Developmental toxicology
- Pharmacology
- Molecular biology
Background:
- Retinoic acid is crucial for embryonic development.
- Disruption of retinoic acid homeostasis is linked to teratogenesis (birth defects).
- Fluconazole is a common antifungal medication with known teratogenic potential.
Purpose of the Study:
- To investigate the effect of fluconazole on the gene expression of cytochrome P450 (CYP) 26 isoforms.
- To understand how fluconazole impacts retinoic acid degradation pathways during embryonic development.
Main Methods:
- ICR pregnant mice were administered a teratogenic dose of fluconazole on gestation day 8.
- Embryos were collected at 12, 24, and 48 hours post-treatment.
- Quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) was used to measure mRNA expression of CYP26a1, CYP26b1, and CYP26c1.
Main Results:
- Fluconazole exposure led to a significant up-regulation of CYP26a1 and CYP26b1 mRNA expression in mouse embryos.
- No significant change in CYP26c1 mRNA expression was observed.
- These findings indicate fluconazole alters the expression of genes critical for retinoic acid metabolism.
Conclusions:
- Fluconazole can disrupt embryonal retinoic acid homeostasis by altering CYP26 gene expression.
- This alteration in retinoic acid metabolism may contribute to the teratogenic effects of fluconazole.
- Further research is warranted to elucidate the precise mechanisms linking fluconazole, CYP26 expression, and birth defects.
