Gestational Alcohol Exposure Altered DNA Methylation Status in the Developing Fetus

Abstract

Ethanol is well known as a teratogenic factor that is capable of inducing a wide range of developmental abnormalities if the developing fetus is exposed to it. Duration and dose are the critical parameters of exposure that affect teratogenic variation to the developing fetus. It is suggested that ethanol interferes with epigenetic processes especially DNA methylation. We aimed to organize all of the available information on the alteration of DNA methylation by ethanol in utero. Thus, we have summarized all published information regarding alcohol-mediated alterations in DNA methylation during gestation. We tried to arrange information in a way that anyone can easily find the alcohol exposure time, doses, sampling time, and major changes in genomic level. Manuscript texts will also represent the correlation between ethanol metabolites and subsequent changes in methylome patterns. We hope that this review will help future researchers to further examine the issues associated with ethanol exposure.

Socioeconomic position during pregnancy and DNA methylation signatures at three stages across early life: epigenome-wide association studies in the ALSPAC birth cohort

“…To assess the robustness of our findings, we ran sensitivity analyses stratified by sex and including additional adjustment: (i) on the possible explanatory variables of SEP: maternal age, 44 body mass index (BMI), 40 , 45 smoking status 46 and alcohol consumption during pregnancy 47 ; (ii) on blood cell composition which were estimated through an established deconvolution approach 48 ; (iii) on delivery mode and self-reported maternal health during the pregnancy; and (iv) for analyses at 7 and 15 years on offspring life course characteristics: own BMI, own use of tobacco and alcohol (only for the analysis at 15 years).…”

Oxidative stress and DNA damage in the mechanism of fetal alcohol spectrum disorders

“…However, the extent of ROS‐mediated direct alterations in developmental signal transduction pathways versus oxidative damage to embryonic and fetal cellular macromolecules like DNA is not known. Here, we discuss the evidence supporting the role of oxidative damage to macromolecules such as DNA, as a pathogenic mechanism involved in EtOH‐initiated embryopathies and neurodevelopmental abnormalities, which is evident at minimally developmentally toxic doses and concentrations of EtOH in various animal models via epigenetic and nonepigenetic mechanisms (Basavarajappa & Subbanna, ; Brooks, ; Galligan et al, ; Haycock, ; Mandal, Halder, Jung, & Chai, ; Miller‐Pinsler et al, ; Miller‐Pinsler & Wells, ; Shapiro et al, ; Shapiro, Miller, & Wells, , Ungerer et al, ; Varadinova & Boyadjieva, ; Tables , Figures & ). For example, a single administration of EtOH to gestational Day 17 pregnant dams increases the level of oxidatively damaged DNA (i.e., 8‐oxoG) in fetal brains of −/− Ogg1 mice lacking OGG1 (the major enzyme that repairs the 8‐oxoG lesion; Miller, Shapiro, Cheng, & Wells, ).…”

Glutathione Protects the Developing Heart from Defects and Global DNA Hypomethylation Induced by Prenatal Alcohol Exposure

“…Many mechanisms have been proposed to explain how PAE disturbs developmental processes. One proposal is that PAE disrupts the normal course of DNA methylation during early development, leading to altered gene expression at a critical stage (Kaminen‐Ahola et al, 2010; Mandal et al, 2017). PAE has been shown to reduce global and specific DNA methylation in whole mouse or rat fetuses, embryos, liver, and brain tissues (Garro et al, 1991; Lussier et al, 2017; Ungerer et al, 2013).…”

“…PAE is known to reduce the substrates and alter the enzymes available for one‐carbon metabolism (OCM) that are critical for DNA methylation. The most abundant and studied form of DNA methylation is the addition of a methyl group to cytosine at position C5 (Mandal et al, 2017). Direct effects of ethanol on the enzymes involved in OCM have been reported in adult tissues (Auta et al, 2017).…”