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Placental Proteomics Reveal Insights into Fetal Alcohol Spectrum Disorders
Katie L Davis-Anderson1, Sebastian Berger2, Emilie R Lunde-Young1
1Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas.
Insights
Chronic alcohol exposure during pregnancy alters placental proteins, impacting fetal development and potentially serving as a diagnostic tool for fetal alcohol spectrum disorders (FASD).
Area of Science:
- Reproductive biology and toxicology
- Proteomics and mass spectrometry
- Developmental neuroscience
Background:
- Fetal alcohol spectrum disorders (FASD) are linked to in utero alcohol exposure, causing neurodevelopmental deficits.
- The placenta's role in FASD etiology and the impact of alcohol on the maternal-fetal interface are underexplored.
- This study investigates the hypothesis that chronic binge alcohol exposure alters placental protein profiles in a rat model.
Purpose of the Study:
- To investigate the effects of chronic binge alcohol exposure on the placental proteome in a rat model.
- To identify specific proteins and pathways altered by gestational alcohol exposure.
- To explore the placenta's potential as a diagnostic tool for fetal alcohol exposure outcomes.
Main Methods:
- Pregnant rats received daily alcohol or isocalorically matched maltose dextrin (controls) via orogastric gavage during specific gestational periods.
- Placentae were collected on gestational day 20, homogenized, and protein lysates were prepared.
- Proteomic analysis was performed using Q Exactive™ Hybrid Quadrupole-Orbitrap™ mass spectrometry for peptide identification and quantification.
Main Results:
- Mass spectrometry identified 2,285 (spectral counts) and 2,000 (intensity-based quantification) placental proteins.
- Forty-five placental proteins were significantly altered by gestational alcohol exposure, including alcohol and aldehyde dehydrogenases.
- Ingenuity analysis revealed ethanol degradation as the most altered canonical pathway and identified impacts on fetal/organ development, with increased risks for metabolic, neurological, and cardiovascular diseases.
Conclusions:
- The placenta is crucial for understanding FASD etiology and may serve as a diagnostic tool for fetal alcohol exposure.
- Placental mass spectrometry provides sophisticated insights into alcohol metabolism enzymes and fetal development regulators.
- Altered placental proteins are linked to pregnancy adaptations, implantation, gestational diseases, fetal organ development, neurodevelopment, and immune functions.
Background:
Fetal alcohol spectrum disorders (FASD) describe many of the well-known neurodevelopmental deficits afflicting children exposed to alcohol in utero. The effects of alcohol on the maternal-fetal interface, especially the placenta, have been less explored. We herein hypothesized that chronic binge alcohol exposure during pregnancy significantly alters the placental protein profile in a rat FASD model.
Methods:
Pregnant rats were orogastrically treated daily with alcohol (4.5 g/kg, gestational day [GD] 5 to 10; 6.0 g/kg, GD 11 to 19) or 50% maltose dextrin (isocalorically matched pair-fed controls). On GD 20, placentae were collected, flash-frozen, and stored until tissues were homogenized. Protein lysates were denatured, reduced, captured on a 10-kDa spin filter, and digested. Peptides were eluted, reconstituted, and analyzed by a Q Exactive™ Hybrid Quadrupole-Orbitrap™ mass spectrometer.
Results:
Mass spectrometry (MS) analysis identified 2,285 placental proteins based on normalized spectral counts and 2,000 proteins by intensity-based absolute quantification. Forty-five placental proteins were significantly (p < 0.05) altered by gestational alcohol exposure by both quantification approaches. These included proteins directly related to alcohol metabolism; specific isoforms of alcohol dehydrogenase and aldehyde dehydrogenase were up-regulated in the alcohol group. Ingenuity analysis identified ethanol degradation as the most significantly altered canonical pathway in placenta, and fetal/organ development as most altered function, with increased risk for metabolic, neurological, and cardiovascular diseases. Physiological roles of the significantly altered proteins were related to early pregnancy adaptations, implantation, gestational diseases, fetal organ development, neurodevelopment, and immune functions.
Conclusions:
We conclude that the placenta is a valuable organ not only to understand FASD etiology but it may also serve as a diagnostic tool to identify novel biomarkers for detecting the outcome of fetal alcohol exposure. Placental MS analysis can offer sophisticated insights into identifying alcohol metabolism-related enzymes and regulators of fetal development.

