The Effects of Early Prenatal Alcohol Exposure on Epigenome and Embryonic Development

Abstract

Prenatal alcohol exposure is one of the most significant causes of developmental disability in the Western world. Maternal alcohol consumption during pregnancy leads to an increased risk of neurological deficits and developmental abnormalities in the fetus. Over the past decade, several human and animal studies have demonstrated that alcohol causes alterations in epigenetic marks, including DNA methylation, histone modifications, and non-coding RNAs. There is an increasing amount of evidence that early pregnancy is a sensitive period for environmental-induced epigenetic changes. It is a dynamic period of epigenetic reprogramming, cell divisions, and DNA replication and, therefore, a particularly interesting period to study the molecular changes caused by alcohol exposure as well as the etiology of alcohol-induced developmental disorders. This article will review the current knowledge about the in vivo and in vitro effects of alcohol exposure on the epigenome, gene regulation, and the phenotype during the first weeks of pregnancy.

Ethanol Effects on Early Developmental Stages Studied Using the Zebrafish

“…Ethanol has detrimental effects on a developing embryo, and the zebrafish is a useful model for a developing human exposed to ethanol in utero (FASD) [ 8 , 25 ]. The range of defects depend on the concentration of ethanol and the timing of exposure, which produce developmental delays, brain defects, heart defects, craniofacial abnormalities, and potential lethality [ 1 , 2 , 9 ]. Ethanol affects transcriptional activity, but there may be independent effects within cells on proteins, protein complexes, lipid membrane structures and other effects.…”

“…Fetal alcohol spectrum disorder (FASD) covers a range of developmental defects and disorders of prenatal alcohol exposure (PAE), which occur when a woman consumes alcohol during their pregnancy [ 1 ]. The consequences of PAE are dependent on many factors, including, amount and duration of alcohol exposure, maternal and fetal age and genetics [ 1 ]. Premature death of the fetus also occurs with PAE [ 1 ].…”

“…The consequences of PAE are dependent on many factors, including, amount and duration of alcohol exposure, maternal and fetal age and genetics [ 1 ]. Premature death of the fetus also occurs with PAE [ 1 ]. Fetal alcohol syndrome (FAS) is the most severe form of the spectrum for babies born following PAE [ 1 ].…”

“…Premature death of the fetus also occurs with PAE [ 1 ]. Fetal alcohol syndrome (FAS) is the most severe form of the spectrum for babies born following PAE [ 1 ]. FAS is characterized by a set of craniofacial dysmorphology, neural defects, cardiac defects, sensory dysfunction, motor disabilities, and learning disabilities [ 2 ].…”

Epigenetics of pregnancy: looking beyond the DNA code

“…Even if there is no specific time point during gestation when alcohol exposure is not accompanied by harmful consequences, the exposure during early embryonic stage is correlated with most severe birth defects [161]. Many researches have also found that alcohol interferes with gene expression levels and epigenetic processes by altering DNA methylation (particularly the expression of two methyltransferase enzymes, DNMT1 and DNMT3A), histone regulation, and non-coding RNAs [162]. Alcohol also induces alterations in the DNA methylome of the hypothalamus, including several differentially methylated regions (DMRs) that could underlie some of the deficits observed in FASD.…”