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Comprehensive Analysis of the Placenta-Cortex Transcriptomic Database Reveals a Neuroactive Ligand-Receptor
Camille Sautreuil1, Maryline Lecointre1, Céline Derambure2,3
1University Rouen Normandie, INSERM U1245, Team Epigenetics and Pathophysiology of Neurodevelopmental Disorders, 76183 Rouen, France.
Prenatal alcohol exposure (PAE) alters gene expression in the placenta and fetal brain, disrupting crucial signaling pathways. This study reveals specific molecular changes that may underlie alcohol-related neurodevelopmental disorders.
Area of Science:
- Neurobiology
- Developmental Biology
- Genomics
Background:
- Neuroplacentology studies the placenta's role in fetal brain development via bioactive molecules.
- Prenatal alcohol exposure (PAE) is known to disrupt gene expression between the placenta and fetal brain.
Purpose of the Study:
- To conduct the first comprehensive, untargeted transcriptomic analysis of PAE's impact on the placenta-cortex axis in mice.
- To identify specific molecular pathways and signaling molecules affected by PAE.
Main Methods:
- Analysis of a murine placenta-cortex transcriptomic database using g:Profiler for functional profiling (Gene Ontology, KEGG, Reactome).
- STRING and ShinyGO analyses for protein-protein interactions and pathway enrichment.
- Validation of selected ligand/receptor candidates via Western blot.
Main Results:
- Identified 21 Gene Ontology, 7 KEGG, and 6 Reactome pathways, with 11 related to cell-cell communication.
- Discovered 38 ligands/receptors from endocrine families, including angiotensinogen, leptin, somatostatin, and PACAP.
- Confirmed PACAP receptor family alterations, showing sex-dependent impacts of PAE.
Conclusions:
- PAE is associated with significant alterations in placenta-cortex transcriptomic profiles.
- Changes in ligands/receptors affect pathways crucial for energy balance, vascular development, and neurogenesis.
- Altered placenta-fetal brain signaling may contribute to alcohol-induced neurodevelopmental disorders.
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