Genomic Alterations in Ethanol-Exposed Trophoblast Cell Lines Induced by Chronic Ethanol Treatment

Abstract

Background: Ethanol consumption during pregnancy results in a broad spectrum of damage, but the knowledge of its mechanism is lacking. Objective: The aim of this study is to determine ethanol-caused genomic alterations in placental cell lines after a repeated ethanol treatment in order to describe new genomic targets of cell damage. Methods: A model of sustained exposure to standard doses of ethanol on two in vitro human choriocarcinoma cell lines, JEG-3 and BeWo, was used. Chromosomic abnormalities and copy number alterations (CNAs) were assessed by G-Banding cytogenetics and oligonucleotide Single Nucleotide Polymorphism-Array analysis (CytoScan, Affymetrix). Results: Chromosomal abnormalities did not change despite ethanol exposure except for the presence of a derivative chromosome 4 [add(4)(p14)] in exposed BeWo cells. Regarding SNP-Array analysis, a total of 21 CNAs were found to be caused by ethanol exposure, 16 in JEG-3 cell line and 5 in BeWo cell line, which were not found in controls. There was no coincidence between JEG-3 and BeWo regions affected by ethanol. Conclusion: Trophoblast cell lines exposed repetitively to ethanol presented genomic instability resulting in CNAs. However, no region has been equally altered in both models to consider it an ethanol exposure target area. So, further studies involving different models and approaches that target gene regulation are required.