Multimodal optical imaging for the assessment of the teratogenic effects of ethanol on zebrafish development.

Abstract

Significance: Prenatal alcohol exposure is a major cause of neurodevelopmental and growth impairments collectively termed fetal alcohol spectrum disorders (FASD). However, the mechanisms by which ethanol disrupts early embryonic development remain incompletely understood; for example, the potential link between ethanol treatment and biomechanical properties of tissues that lead to defects in development is not understood.

Aim: To address this gap in knowledge, we used zebrafish (Danio rerio), a powerful vertebrate model with optical transparency and rapid development, to investigate ethanol-induced alterations during embryogenesis.

Approach: Embryos were exposed to varying concentrations of ethanol and assessed using a multimodal imaging approach integrating light sheet fluorescence microscopy, optical coherence tomography, and optical coherence elastography.

Results: This platform enabled high-resolution, noninvasive, and parallel visualization of structural, molecular, and biomechanical changes. We found that ethanol exposure disrupts Wnt ligand expression in the nervous system, which correlates with a cascade of morphological abnormalities consistently detected across imaging modalities and consistent with alterations to $\mathrm{Wnt}/\beta$ -catenin signaling activity.

Conclusions: These findings highlight the critical role of $\mathrm{Wnt}/\beta$ -catenin signaling in alcohol-induced teratogenesis and underscore the value of zebrafish models and multimodal imaging for advancing our understanding of FASD pathogenesis.