ArticleDisease models & mechanisms
Ethanol induces embryonic malformations by competing for retinaldehyde dehydrogenase activity during vertebrate gastrulation.
Article in Disease models & mechanisms. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 100 citations in OpenAlex.
- Folic acid prevention of neural tube defects requires retinoic acid produced by ALDH1L1.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Developmental Neurotoxicity of Alcohol from Neuronal Basis to Behavioural Outcomes: A Comprehensive Review.Neurology international · 2026Review
- The Role of the Hedgehog Pathway in Alcohol-Induced Birth Defects.Advances in experimental medicine and biology · 2026Review
- Prevalence of congenital heart defects among children with and without diagnosed fetal alcohol spectrum disorders, 2016-2022.Drug and alcohol dependence · 2025Article
- Cannabidiol exerts teratogenic effects on developing zebrafish through the sonic hedgehog signaling pathway.Scientific reports · 2025Article
- In Vitro Models of Cardiovascular Disease: Embryoid Bodies, Organoids and Everything in Between.Biomedicines · 2024Review
- Analysis of alcohol-metabolizing enzymes genetic variants and RAR/RXR expression in patients diagnosed with fetal alcohol syndrome: a case-control study.BMC genomics · 2024Article
- Potential Effects of Low-Level Toluene Exposure on the Nervous System of Mothers and Infants.International journal of molecular sciences · 2024Article
- Risk and Resilience Variants in the Retinoic Acid Metabolic and Developmental Pathways Associated with Risk of FASD Outcomes.Biomolecules · 2024Article
- Alcohol induces neural tube defects by reducing retinoic acid signaling and promoting neural plate expansion.Frontiers in cell and developmental biology · 2023Article
- Genetically programmed retinoic acid deficiency during gastrulation phenocopies most known developmental defects due to acute prenatal alcohol exposure in FASD.Frontiers in cell and developmental biology · 2023Article
- Gene-alcohol interactions in birth defects.Current topics in developmental biology · 2023Article
- Disruption of vitamin A homeostasis by the biocide tetrakis(hydroxymethyl) phosphonium sulphate in pregnant rabbits.Journal of applied toxicology : JAT · 2022Article
- Effect of Embryonic Alcohol Exposure on Craniofacial and Skin Melanocyte Development: Insights from Zebrafish (Toxics · 2022Article
- Retinoic Acid is Required for Normal Morphogenetic Movements During Gastrulation.Frontiers in cell and developmental biology · 2022Article
- Reduced Retinoic Acid Signaling During Gastrulation Induces Developmental Microcephaly.Frontiers in cell and developmental biology · 2022Article
- Zebrafish models of fetal alcohol spectrum disorders.Genesis (New York, N.Y. : 2000) · 2021Review
- Review
- Retinoic Acid Fluctuation Activates an Uneven, Direction-Dependent Network-Wide Robustness Response in Early Embryogenesis.Frontiers in cell and developmental biology · 2021Article
- Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human embryos exposed to alcohol (ethanol) develop a complex developmental phenotype known as fetal alcohol spectrum disorder (FASD). In Xenopus embryos, ethanol reduces the levels of retinoic acid (RA) signaling during gastrulation. RA, a metabolite of vitamin A (retinol), is required for vertebrate embryogenesis, and deviation from its normal levels results in developmental malformations. Retinaldehyde dehydrogenase 2 (RALDH2) is required to activate RA signaling at the onset of gastrulation. We studied the effect of alcohol on embryogenesis by manipulating retinaldehyde dehydrogenase activity in ethanol-treated embryos. In alcohol-treated embryos, we analyzed RA signaling levels, phenotypes induced and changes in gene expression. Developmental defects that were characteristic of high ethanol concentrations were phenocopied by a low ethanol concentration combined with partial RALDH inhibition, whereas Raldh2 overexpression rescued the developmental malformations induced by high ethanol. RALDH2 knockdown resulted in similar RA signaling levels when carried out alone or in combination with ethanol treatment, suggesting that RALDH2 is the main target of ethanol. The biochemical evidence that we present shows that, at the onset of RA signaling during early gastrulation, the ethanol effect centers on the competition for the available retinaldehyde dehydrogenase activity. In light of the multiple regulatory roles of RA, continued embryogenesis in the presence of abnormally low RA levels provides an etiological explanation for the malformations observed in individuals with FASD.
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