Interaction between retinoic acid and FGF/ERK signals are involved in Dexamethasone-induced abnormal myogenesis during embryonic development

Despite the common application in pregnancy at clinical practice, it remains ambiguous whether dexamethasone (Dex) exposure can affect embryonic myogenesis. In this study, firstly we showed that 10(-6) M Dex (Cheng et al., 2016; 2017) treatment resulted in abnormal myogenesis in chicken embryos. Secondly, we demonstrated that 10-6 M Dex-induced abnormality of myogenesis resulted from aberrant cell proliferation, as well as from alteration of the differentiation process from the early stage of somitogenesis up to the late stage of myogenesis. The above-mentioned results caused by Dex exposure might be due to the aberrant gene expressions of somite formation (Raldh2, Fgf8, Wnt3a, beta-catenin, Slug, Paraxis, N-cadherin) and differentiation (Pax3, MyoD, Wnt3a, Msx1, Shh). Thirdly, RNA sequencing implied the statistically significant differential gene expressions in regulating the myofibril and systemic development, as well as a dramatical alteration of retinoic acid (RA) signaling during somite development in the chicken embryos exposed to Dex. The subsequent validation experiments verified that Dex treatment indeed led to a metabolic change of RA signaling, which was up-regulated and principally mediated by FGF-ERK signaling revealed by means of the combination of chicken embryos and in vitro C2C12 cells. These findings highlight that 10(-6) M Dex exposure enhances the risk of abnormal myogenesis through interfering with RA signaling during development.

Automated summary

This study demonstrates that exposure to 10(-6) M Dex can lead to abnormal myogenesis in chicken embryos, mainly due to aberrant cell proliferation and changes in gene expression related to somite formation and differentiation. RNA sequencing revealed significant differential gene expressions in regulating myofibril development and systemic development, as well as dramatic alterations in retinoic acid (RA) signaling during somite development in chicken embryos exposed to Dex. Further experiments confirmed that Dex treatment affects RA signaling and is principally mediated by FGF-ERK signaling.