RT Journal Article
SR Electronic
T1 Ethanol exposure model in zebrafish causes phenotypic, behavioral and gene expression changes that mimic Fetal Alcohol Spectrum Disorders in human birth cohorts
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2024.08.05.606708
DO 10.1101/2024.08.05.606708
A1 Yilmaz, Elanur
A1 Nelson, Nastasia
A1 Tosto, Giuseppe
A1 Carter, R. Colin
A1 Kizil, Caghan
YR 2024
UL http://biorxiv.org/content/early/2024/08/07/2024.08.05.606708.abstract
AB Fetal Alcohol Spectrum Disorders (FASD) represent a significant global health challenge, characterized by physical and neurodevelopmental abnormalities in offspring resulting from prenatal alcohol exposure. This study aims to utilize the zebrafish to examine the phenotypic, behavioral, and molecular changes associated with embryonic ethanol exposure, providing a model for human FASD conditions. Our study exposed zebrafish embryos to 0.5% ethanol during a critical developmental window (2-24 hours post-fertilization) and documented significant craniofacial and cardiac deformities, which recapitulate what has been observed in human FASD in humans. Notably, exposed zebrafish exhibited reduced skull and eye sizes, thickened jaw size, and enlarged heart chambers. We found reduced burst swim distance following a touch stimulus, a novel behavioral assessment of potential deficits in sensory processing such as processing speed and/or stress/startle response, both of which are affected in human FASD. Whole-organism gene expression was found to be altered by ethanol for orthologs of four of five inflammation-related genes for which placental expression was previously found to be altered in response to alcohol in human placentas (SERPINE1, CRHB, BCL2L1, PSMB4, PTGS2A). We conclude that the zebrafish model effectively mimics several FASD phenotypes observed in humans, confirming gene expression changes we have previously documented in a human observational study and providing a valuable platform for exploring the underlying mechanisms of alcohol-induced embryonic alterations and for developing diagnostic markers and therapeutic targets for early intervention.Competing Interest StatementThe authors have declared no competing interest.