Evaluation of fetal skeletal malformations in deoxynivalenol-treated mice using microarray analysis

Area of Science:

• Toxicology
• Developmental Biology
• Genetics

Background:

• Deoxynivalenol (DON), a trichothecene mycotoxin from Fusarium, is prevalent in global cereal foods.
• DON exposure causes various toxic effects, including impaired fetal development and skeletal malformations.
• The precise molecular mechanisms underlying DON-induced teratogenicity remain incompletely understood.

Purpose of the Study:

• To investigate fetal skeletal malformations in mice exposed to DON during gestation.
• To identify genes and pathways affected by maternal DON exposure using microarray analysis.
• To validate the expression changes of specific genes involved in skeletal development.

Main Methods:

• Maternal mice were exposed to DON, and fetal skeletal development was assessed.
• Microarray analysis was performed on fetal vertebral bones to identify differentially expressed genes.
• Real-time reverse transcription-Polymerase Chain Reaction (RT-PCR) was used to validate gene expression changes.

Main Results:

• DON exposure resulted in diverse fetal skeletal defects, including vertebral and rib anomalies, and polydactyly.
• Microarray analysis revealed abnormal expression of 282 genes in fetal vertebral bones, categorized into skeletal development, carcinogenesis, and embryogenesis, among others.
• RT-PCR confirmed significant upregulation of fibrillin-1, Col9A2, PAPSS2, and Pax1, and downregulation of Runx2 and PTHLH mRNA levels.

Conclusions:

• Maternal DON exposure induces significant fetal skeletal deformities in mice.
• Altered expression of specific genes, particularly those related to bone development, is implicated in DON-induced teratogenicity.
• These identified genes represent potential targets for further research into DON toxicity and skeletal development.