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

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.

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.

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.

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.

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.