Usage of Dexamethasone Increases the Risk of Cranial Neural Crest Dysplasia in the Chick Embryo

Xin Cheng, He Li, Yu Yan, Guang Wang, Zachary Berman, Manli Chuai, Xuesong Yang (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
73 Downloads (Pure)

Abstract

Dexamethasone (Dex) is commonly used in the treatment of a variety of benign and malignant conditions. Unfortunately, although it has a variety of teratogenic effects, it remains used in clinical practice for pregnant women mainly due to limited alternatives. However, there is limited knowledge of the mechanisms that lead to the observed teratogenic effects. In this study, the effects of Dex during embryogenesis on neural crest development were evaluated in the early chick embryos. First, we demonstrated that 100µL 10-6 M Dex treatment leads to craniofacial developmental defects, and also retards embryo growth and plausibly can cause embryo demise. Second, we demonstrated that Dex represses the production of HNK-1, PAX7 and AP-2α labeled cranial neural crest cells (CNCCs), the progenitor cells of the craniofacial skeleton. Third, double immunofluorescent staining of pHIS3/PAX7 and AP-2α/c-Caspase3 revealed that Dex promotes cell apoptosis but does not change cell proliferation rates. Last, FGF signaling molecules were inhibited by Dex treatment. Dex also inhibited NCCs production by repressing Msx1 expression in the developing neural tube and by altering expression of epithelial-mesenchymal transition-related adhesion molecules and cell migration genes. Overall, we obtained experimental evidence that Dex treatment during embryogenesis disrupts cranial neural crest (CNC) development which in turn causes defective cranial bone development.

Original languageEnglish
Pages (from-to)36-47
Number of pages12
JournalToxicological Sciences
Volume158
Issue number1
Early online date27 Apr 2017
DOIs
Publication statusPublished - 27 Apr 2017

Keywords

  • Journal article
  • Dexamethasone (Dex)
  • Cranial neural crest (CNC)
  • Skeletogenesis
  • Fgf

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