ArticleScientific reports2018
Acetaldehyde inhibits retinoic acid biosynthesis to mediate alcohol teratogenicity.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 71 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
- Effects of ethanol exposure in neonatal mice on retinoic acid signaling in forebrain neurons and astrocytes.IBRO neuroscience reports · 2026Article
- Molecular Regulation of Palatogenesis and Clefting: An Integrative Analysis of Genetic, Epigenetic Networks, and Environmental Interactions.International journal of molecular sciences · 2025Review
- 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
- Risk and Resilience Variants in the Retinoic Acid Metabolic and Developmental Pathways Associated with Risk of FASD Outcomes.Biomolecules · 2024Article
- Fetal alcohol spectrum disorders.Nature reviews. Disease primers · 2023Review
- Alcohol and breast cancer.Pharmacological reports : PR · 2023Review
- Alcohol induces neural tube defects by reducing retinoic acid signaling and promoting neural plate expansion.Frontiers in cell and developmental biology · 2023Article
- Effects of retinoic acid receptor α modulators on developmental ethanol-induced neurodegeneration and neuroinflammation.Frontiers in neuroscience · 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
- Disruption of vitamin A homeostasis by the biocide tetrakis(hydroxymethyl) phosphonium sulphate in pregnant rabbits.Journal of applied toxicology : JAT · 2022Article
- Enhanced Loss of Retinoic Acid Network Genes inCells · 2022Article
- Retinoic Acid is Required for Normal Morphogenetic Movements During Gastrulation.Frontiers in cell and developmental biology · 2022Article
- E-liquids and vanillin flavoring disrupts retinoic acid signaling and causes craniofacial defects in Xenopus embryos.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
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Alcohol consumption during pregnancy induces Fetal Alcohol Spectrum Disorder (FASD), which has been proposed to arise from competitive inhibition of retinoic acid (RA) biosynthesis. We provide biochemical and developmental evidence identifying acetaldehyde as responsible for this inhibition. In the embryo, RA production by RALDH2 (ALDH1A2), the main retinaldehyde dehydrogenase expressed at that stage, is inhibited by ethanol exposure. Pharmacological inhibition of the embryonic alcohol dehydrogenase activity, prevents the oxidation of ethanol to acetaldehyde that in turn functions as a RALDH2 inhibitor. Acetaldehyde-mediated reduction of RA can be rescued by RALDH2 or retinaldehyde supplementation. Enzymatic kinetic analysis of human RALDH2 shows a preference for acetaldehyde as a substrate over retinaldehyde. RA production by hRALDH2 is efficiently inhibited by acetaldehyde but not by ethanol itself. We conclude that acetaldehyde is the teratogenic derivative of ethanol responsible for the reduction in RA signaling and induction of the developmental malformations characteristic of FASD. This competitive mechanism will affect tissues requiring RA signaling when exposed to ethanol throughout life.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.