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Updated: Dec 12, 2025
Quantification of Ethanol Levels in Zebrafish Embryos Using Head Space Gas Chromatography
Published on: February 11, 2020
Multifactorial Genetic and Environmental Hedgehog Pathway Disruption Sensitizes Embryos to Alcohol-Induced
Joshua L Everson1,2, Rithik Batchu1, Johann K Eberhart1,2
1From the Department of Molecular Biosciences, School of Natural Sciences, University of Texas at Austin, Austin, Texas, USA.
Insights
Prenatal alcohol exposure (PAE) can cause birth defects. Genetic and environmental factors, like pesticide exposure, interact to worsen these defects, particularly in the developing face.
Area of Science:
- Developmental Biology
- Toxicology
- Genetics
Background:
- Prenatal alcohol exposure (PAE) is a leading environmental cause of birth defects, including facial abnormalities known as fetal alcohol spectrum disorders (FASD).
- The wide variation in FASD outcomes suggests that genetic and environmental factors interact to modify PAE's effects.
- The Hedgehog (Hh) signaling pathway is implicated in craniofacial development and may modify ethanol's teratogenicity, with key components like Smoothened susceptible to environmental chemicals.
Purpose of the Study:
- To investigate multifactorial genetic and environmental interactions in craniofacial development using a zebrafish model.
- To explore how disruption of the Hedgehog signaling pathway influences susceptibility to alcohol- and pesticide-induced facial defects.
Main Methods:
- Utilized a zebrafish model to study craniofacial development.
- Examined the effects of alcohol exposure and piperonyl butoxide (PBO) on zebrafish embryos.
- Assessed the impact of genetic alterations in the shha gene (Hedgehog pathway) on susceptibility to teratogens.
Main Results:
- Loss of a single shha allele sensitized zebrafish embryos to alcohol- and PBO-induced facial defects.
- Co-exposure to PBO and alcohol demonstrated a synergistic effect, increasing the frequency and severity of facial defects.
- Genetically susceptible shha heterozygotes exhibited more profound defects upon co-exposure to PBO and alcohol.
Conclusions:
- Findings highlight the multifactorial basis of alcohol-induced craniofacial defects.
- Genetic disruption of the Hh pathway is implicated in alcohol teratogenicity.
- Co-exposure to environmental chemicals like PBO, which affect Hh signaling, may be significant factors in FASD and related craniofacial disorders.
Background:
Prenatal alcohol exposure (PAE) is perhaps the most common environmental cause of human birth defects. These exposures cause a range of structural and neurological defects, including facial dysmorphologies, collectively known as fetal alcohol spectrum disorders (FASD). While PAE causes FASD, phenotypic outcomes vary widely. It is thought that multifactorial genetic and environmental interactions modify the effects of PAE. However, little is known of the nature of these modifiers. Disruption of the Hedgehog (Hh) signaling pathway has been suggested as a modifier of ethanol teratogenicity. In addition to regulating the morphogenesis of craniofacial tissues commonly disrupted in FASD, a core member of the Hh pathway, Smoothened, is susceptible to modulation by structurally diverse chemicals. These include environmentally prevalent teratogens like piperonyl butoxide (PBO), a synergist found in thousands of pesticide formulations.
Methods:
Here, we characterize multifactorial genetic and environmental interactions using a zebrafish model of craniofacial development.
Results:
We show that loss of a single allele of shha sensitized embryos to both alcohol- and PBO-induced facial defects. Co-exposure of PBO and alcohol synergized to cause more frequent and severe defects. The effects of this co-exposure were even more profound in the genetically susceptible shha heterozygotes.
Conclusions:
Together, these findings shed light on the multifactorial basis of alcohol-induced craniofacial defects. In addition to further implicating genetic disruption of the Hh pathway in alcohol teratogenicity, our findings suggest that co-exposure to environmental chemicals that perturb Hh signaling may be important variables in FASD and related craniofacial disorders.
