Paternal Alcohol Exposure Affects Sperm Cytosine Methyltransferase Messenger RNA Levels

Bielawski, Dawn M.; Zaher, Fadi M.; Svinarich, David M.; Abel, Ernest L.

doi:10.1111/j.1530-0277.2002.tb02544.x

Cited by 116 publications

(44 citation statements)

References 24 publications

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“…They are, however, in contrast with another study which indicated that ethanol exposure resulted in an increased DNMT activity as well as hyper methylation and decreased expression of cell cycle genes in neural stem cells (NSCs) [60]. Despite this observation, and consistent with our data, the Dnmt-1 transcript was down-regulated by alcohol in both neural stem cells [60] and rat sperm [61]. Numerous studies have reported the effects of ethanol exposure on gene expression [29,62–69].…”

Section: Discussionsupporting

confidence: 79%

Alcohol modulates expression of DNA methyltranferases and methyl CpG-/CpG domain-binding proteins in murine embryonic fibroblasts

Mukhopadhyay

Rezzoug

Kaikaus

et al. 2013

Reproductive Toxicology

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Fetal alcohol syndrome (FAS), presenting with a constellation of neuro-/psychological, craniofacial and cardiac abnormalities, occurs frequently in offspring of women who consume alcohol during pregnancy, with a prevalence of 1–3 per 1000 livebirths. The present study was designed to test the hypothesis that alcohol alters global DNA methylation, and modulates expression of the DNA methyltransferases (DNMTs) and various methyl CpG-binding proteins. Murine embryonic fibroblasts (MEFs), utilized as an in vitro embryonic model system, demonstrated ~5% reduction in global DNA methylation following exposure to 200 mM ethanol. In addition, ethanol induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway. Such degradation could be completely rescued by pretreatment of MEF cells with the proteasomal inhibitor, MG-132. These data support a potential epigenetic molecular mechanism underlying the pathogenesis of FAS during mammalian development.

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Section: Discussionsupporting

confidence: 79%

Alcohol modulates expression of DNA methyltranferases and methyl CpG-/CpG domain-binding proteins in murine embryonic fibroblasts

Mukhopadhyay

Rezzoug

Kaikaus

et al. 2013

Reproductive Toxicology

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“…As discussed in Section 4, alcohol is known to affect methylation machinery, leading to severe health consequences, such as cancer (Varela-Rey et al, 2013). Particularly, alcohol has been shown to decrease activity of DNMT1 in somatic tissue (Ponomarev et al, 2012) and reduce cytosine methyltransferase mRNA in sperm (Bielawski, Zaher, Svinarich, & Abel, 2002). Alcohol is also known to reduce levels of the methyl donor SAM, leading to hypomethylation of somatic tissue (Lu & Mato, 2005).…”

Section: Possible Mechanisms For Germline-dependent Epigenetic Inhmentioning

confidence: 99%

Alcohol effects on the epigenome in the germline: Role in the inheritance of alcohol-related pathology

Chastain

Sarkar

2017

Alcohol

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Excessive alcohol exposure has severe health consequences, and clinical and animal studies have demonstrated that disruptions in the epigenome of somatic cells, such as those in brain, are an important factor in the development of alcohol-related pathologies, such as alcohol-use disorders (AUDs) and fetal alcohol spectrum disorders (FASDs). It is also well known that alcohol-related health problems are passed down across generations in human populations, but the complete mechanisms for this phenomenon are currently unknown. Recent studies in animal models have suggested that epigenetic factors are also responsible for the transmission of alcohol-related pathologies across generations. Alcohol exposure has been shown to induce changes in the epigenome of sperm of exposed male animals, and these epimutations are inherited in the offspring. This paper reviews evidence for multigenerational and transgenerational epigenetic inheritance of alcohol-related pathology through the germline. We also review the literature on the epigenetic effects of alcohol exposure on somatic cells in brain, and its contribution to AUDs and FASDs. We note gaps in knowledge in this field, such as the lack of clinical studies in human populations and the lack of data on epigenetic inheritance via the female germline, and we suggest future research directions.

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“…A comprehensive list of the ethanol exposures used and primary findings of these studies is shown in Table 1. Several groups have found that paternal ethanol induces physiologic abnormalities in offspring in the absence of maternal ethanol exposure, including low birth weight (Bielawski, Zaher, Svinarich, & Abel, 2002; Ledig et al, 1998), increased number of runts (Bielawski & Abel, 1997; Bielawski et al, 2002), altered organ weights (Abel, 1993b; Ledig et al, 1998; Lee et al, 2013), thickening of layers of the cerebral cortex (Jamerson, Wulser, & Kimler, 2004), and low testosterone levels (Abel, 1989b). Several behavioral abnormalities have also been noted, including decreased spatiotemporal learning (Wozniak, Cicero, Kettinger, & Meyer, 1991), decreased novelty-seeking behavior (Ledig et al, 1998), increased immobility on the forced-swim test (Abel & Bilitzke, 1990; Liang et al, 2014), and decreased grooming (Abel, 1991a).…”

Section: Effects Of Paternal Ethanol Exposure On Offspringmentioning

confidence: 99%

“…Ethanol gavage 3 times per week for 9 weeks in rats was associated with decreased expression of the maintenance methyltransferase DNMT1 in sperm (Bielawski et al, 2002). Locus-specific studies have focused on the effect of ethanol consumption on DNA methylation at heavily methylated, imprinted regions in sperm that are resistant to genome-wide demethylation.…”

Section: How Does Ethanol Modify Heritable Variants In Germ Cells?mentioning

confidence: 99%

Drinking beyond a lifetime: New and emerging insights into paternal alcohol exposure on subsequent generations

Finegersh

Rompala

Martin³

et al. 2015

Alcohol

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Alcohol-use disorder (AUD) is prevalent and associated with substantial socioeconomic costs. While heritability estimates of AUD are ~50%, identifying specific gene variants associated with risk for AUD has proven challenging despite considerable investment. Emerging research into heritability of complex diseases has implicated transmission of epigenetic variants in the development of behavioral phenotypes, including drug preference and drug-induced behavior. Several recent rodent studies have specifically focused on paternal transmission of epigenetic variants, which is especially relevant because sires are not present for offspring rearing and changes to offspring phenotype are assumed to result from modifications to the sperm epigenome. While considerable interest in paternal transmission of epigenetic variants has emerged recently, paternal alcohol exposures have been studied for 30+ years with interesting behavioral and physiologic effects noted on offspring. However, only recently, with improvements in technology to identify epigenetic modifications in germ cells, has it been possible to identify mechanisms by which paternal ethanol exposure alters offspring behavior. This review presents an overview of epigenetic inheritance in the context of paternal ethanol exposure and suggests future studies to identify specific effects of paternal ethanol exposure on offspring behavior and response to ethanol.

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Paternal Alcohol Exposure Affects Sperm Cytosine Methyltransferase Messenger RNA Levels

Abstract: Alcohol-induced reductions in cytosine methyltransferase mRNA levels may reflect altered genomic imprinting caused by reduced DNA methylation, which, in turn, may lead to the expression of normally silent paternal alleles and may be a mechanism for paternal alcohol effects.

Cited by 116 publications

References 24 publications

Alcohol modulates expression of DNA methyltranferases and methyl CpG-/CpG domain-binding proteins in murine embryonic fibroblasts

Alcohol modulates expression of DNA methyltranferases and methyl CpG-/CpG domain-binding proteins in murine embryonic fibroblasts

Alcohol effects on the epigenome in the germline: Role in the inheritance of alcohol-related pathology

Drinking beyond a lifetime: New and emerging insights into paternal alcohol exposure on subsequent generations

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