A transcriptome meta-analysis of ethanol embryonic exposure: Implications in neurodevelopment and neuroinflammatory genes

Abstract

Fetal Alcohol Spectrum Disorder (FASD) comprises the phenotypes induced by prenatal alcohol exposure. Understanding the molecular mechanisms of FASD is needed since it is a public health problem. This study aimed to evaluate the impact of ethanol in the differential gene expression (DGE) of embryonic cells and fetal tissues by performing a transcriptome meta-analysis in microarrays datasets publicly available. The datasets were obtained in the GEO database and DGE was evaluated, followed by meta-analysis. DGE was also analyzed in a RNA-Seq dataset, although it was not included in the meta-analysis. To filter the main candidate genes, a database and literature review was performed, followed by ontologies enrichment analyses. In the meta-analysis, 1,938 genes were deregulated and 487 were perturbed in the RNA-Seq. Calcium homeostasis and neuroinflammation genes were overrepresented in the meta-analysis and RNA-Seq, respectively. After the database and literature review, DOCK8, FOXG1, IL1RN, and PRKN genes were proposed as new candidates for FASD; they are associated with neurodevelopment and neuroinflammation. BDNF and SLC2A1, previously associated to FASD, were also suggested in meta-analysis as candidate genes. It is known neuroinflammation reduction might help to minimize the alcohol damage. Hence, there is an urgent need to understand FASD molecular mechanisms to help in strategies aimed at preventing ethanol-induced neurologic damage.

Keywords

• Prenatal ethanol exposure
• Fetal alcohol spectrum disorder
• Differential gene expression
• Neurophenotypes
• Random effect model
• Microarray