Epigenetic mediators and consequences of excessive alcohol consumption

Mahnke, Amanda H.; Miranda, Rajesh C.; Homanics, Gregg E.

doi:10.1016/j.alcohol.2017.02.357

Cited by 31 publications

(21 citation statements)

References 77 publications

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“…The postulated mechanisms underlying EtOH‐initiated teratogenicity are complex, and include: hypoxia (Bosco & Diaz, ); nutritional deficiencies (Bastons‐Compta, Astals, Andreu‐Fernandez, Navarro‐Tapia, & Garcia‐Algar, ; Muralidharan, Sarmah, Zhou, & Marrs, ); alterations in epigenetic changes via alterations in histone and DNA marks, effects on the activity of readers, writers and erasers of these marks, and on noncoding RNAs (Basavarajappa & Subbanna, ; Mahnke, Miranda, & Homanics, ; Muralidharan et al, ; Portales‐Casamar et al, ; Veazey, Parnell, Miranda, & Golding, ); protein alterations affecting both cellular energy and signal transduction pathways (Li et al, ; Zhou, ) as well as cell–cell interactions and cell adhesion (Arevalo et al, ); deregulation or alteration of cellular processes (e.g., apoptosis (Muralidharan et al, ), neurotransmission (Vangipuram & Lyman, ), growth factors and trophic support (Kane et al, ), impairment to the blood brain barrier (Nakhoul, Seif, Haddad, & Haddad, ); and oxidative stress which may further contribute to alterations in the above pathways (Muralidharan et al, ; Wells et al, ; Figure ). It is likely that multiple mechanisms contribute to FASD, and the identification of specific mechanisms may be confounded by a variety of factors, including the dose of EtOH used in vivo , concentrations used in embryo culture, and the timing and duration of exposure (Kleiber et al, ).…”

Section: Context: Overview Of Mechanisms Postulated To Be Involved Inmentioning

confidence: 99%

“…In humans, a variety of other factors may confound the results even further. These include genetic and epigenetic predisposition to the negative effects of alcohol, maternal body weight and age, nutrition and lifestyle, exposure to other drugs/medications, and comorbidities involving oxidative stress such as cardiovascular diseases, diabetes, and so on (Ehrhart et al, ; Lunde et al, ; Lussier et al, ; Mahnke et al, ). The mechanisms involved in FASD, including EtOH‐induced genomic and epigenetic dysregulation, may depend on the factors listed above, and may result in differences in results seen in different laboratories, involving different mechanisms, which may become increasingly complex with higher doses/concentrations and extended gestational exposure (Tables ).…”

Section: Context: Overview Of Mechanisms Postulated To Be Involved Inmentioning

confidence: 99%

“…In addition, environmental factors such as exposure to cadmium may also reduce OGG1 protein levels (Youn et al, ). Although numerous epigenetic modifications have been associated with in utero EtOH exposure (Galligan et al, ; Haycock, ; Lussier et al, ; Mahnke et al, ; Melnyk et al, ; Starkman, Sakharkar, & Pandey, ; Ungerer, Knezovich, & Ramsay, ), it is not known which modifications and specific genes are involved in the mechanism of FASD. However, studies of EtOH‐initiated epigenetic modifications specific to Ogg1 knockout (KO) progeny suggest selective OGG1‐dependent modifications, which are likely to reflect potentially pathogenic modifications (Bhatia & Wells, ).…”

Section: Ros In Etoh‐initiated Birth Defects and Postnatal Neurodevelmentioning

confidence: 99%

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

Bhatia

Drake

Miller

et al. 2019

Birth Defects Research

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This review covers molecular mechanisms involving oxidative stress and DNA damage that may contribute to morphological and functional developmental disorders in animal models resulting from exposure to alcohol (ethanol, EtOH) in utero or in embryo culture. Components covered include: (a) a brief overview of EtOH metabolism and embryopathic mechanisms other than oxidative stress; (b) mechanisms within the embryo and fetal brain by which EtOH increases the formation of reactive oxygen species (ROS); (c) critical embryonic/fetal antioxidative enzymes and substrates that detoxify ROS; (d) mechanisms by which ROS can alter development, including ROS-mediated signal transduction and oxidative DNA damage, the latter of which leads to pathogenic genetic (mutations) and epigenetic changes; (e) pathways of DNA repair that mitigate the pathogenic effects of DNA damage; (f) related indirect mechanisms by which EtOH enhances risk, for example by enhancing the degradation of some DNA repair proteins; and, (g) embryonic/fetal pathways like NRF2 that regulate the levels of many of the above components. Particular attention is paid to studies in which chemical and/or genetic manipulation of the above mechanisms has been shown to alter the ability of EtOH to adversely affect development. Alterations in the above components are also discussed in terms of: (a) individual embryonic and fetal determinants of risk and (b) potential risk biomarkers and mitigating strategies. FASD risk is likely increased in progeny which/who are biochemically predisposed via genetic and/or environmental mechanisms, including enhanced pathways for ROS formation and/or deficient pathways for ROS detoxification or DNA repair.

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Section: Context: Overview Of Mechanisms Postulated To Be Involved Inmentioning

confidence: 99%

Section: Context: Overview Of Mechanisms Postulated To Be Involved Inmentioning

confidence: 99%

Section: Ros In Etoh‐initiated Birth Defects and Postnatal Neurodevelmentioning

confidence: 99%

See 1 more Smart Citation

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

Bhatia

Drake

Miller

et al. 2019

Birth Defects Research

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“…18,23 The long-term persistence of FASD growth defects and emerging association with the development of chronic disease later in life, suggest alcohol has the capacity to heritably disrupt fundamental aspects of epigenetic programming. [24][25][26][27][28] These observations suggest a potential association between preconception male alcohol exposure, altered epigenetic programming in sperm, and the development of FASD-associated growth defects in the offspring. In support of this assertion, animal models of paternal alcohol exposure report alterations in the control of key enzymes regulating chromatin structure as well as changes in the DNA methylation profiles of alcohol-exposed sperm.…”

Section: Introductionmentioning

confidence: 99%

DNA methylation-independent growth restriction and altered developmental programming in a mouse model of preconception male alcohol exposure

et al. 2017

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The preconception environment is a significant modifier of dysgenesis and the development of environmentally-induced disease. To date, fetal alcohol spectrum disorders (FASDs) have been exclusively associated with maternal exposures, yet emerging evidence suggests male-inherited alterations in the developmental program of sperm may be relevant to the growth-restriction phenotypes of this condition. Using a mouse model of voluntary consumption, we find chronic preconception male ethanol exposure associates with fetal growth restriction, decreased placental efficiency, abnormalities in cholesterol trafficking, sex-specific alterations in the genetic pathways regulating hepatic fibrosis, and disruptions in the regulation of imprinted genes. Alterations in the DNA methylation profiles of imprinted loci have been identified in clinical studies of alcoholic sperm, suggesting the legacy of paternal drinking may transmit via heritable disruptions in the regulation of imprinted genes. However, the capacity of sperm-inherited changes in DNA methylation to broadly transmit environmentally-induced phenotypes remains unconfirmed. Using bisulphite mutagenesis and second-generation deep sequencing, we find no evidence to suggest that these phenotypes or any of the associated transcriptional changes are linked to alterations in the sperm-inherited DNA methylation profile. These observations are consistent with recent studies examining the male transmission of diet-induced phenotypes and emphasize the importance of epigenetic mechanisms of paternal inheritance beyond DNA methylation. This study challenges the singular importance of maternal alcohol exposures and suggests paternal alcohol abuse is a significant, yet overlooked epidemiological factor complicit in the genesis of alcohol-induced growth defects, and may provide mechanistic insight into the failure of FASD children to thrive postnatally.

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“…In addition, dynamic epigenetic mechanisms such as histone modifications, changes in DNA methylation, chromatin remodeling, and non-coding RNAs signaling, play a significant role in stem-cell control of self-renewal and differentiation into tissue-specific lineages [145]. Alcohol metabolism has a profound impact on cellular gene expression via modification in the epigenetic machinery [119, 146, 147]. Extensive epigenetic alteration subsequent to alcohol exposure may interfere with the molecular switches needed for the coordinated process of stem cell differentiation.…”

Section: Alcohol Toxicity On Stem Cells: In Search For Molecular Mechmentioning

confidence: 99%

Stem cells under the influence of alcohol: effects of ethanol consumption on stem/progenitor cells

Rocco

Baldari

Pani³

et al. 2018

Cell. Mol. Life Sci.

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Stem cells drive embryonic and fetal development. In several adult tissues, they retain the ability to self-renew and differentiate into a variety of specialized cells, thus contributing to tissue homeostasis and repair throughout life span. Alcohol consumption is associated with an increased risk for several diseases and conditions. Growing and developing tissues are particularly vulnerable to alcohol’s influence, suggesting that stem- and progenitor-cell function could be affected. Accordingly, recent studies have revealed the possible relevance of alcohol exposure in impairing stem-cell properties, consequently affecting organ development and injury response in different tissues. Here, we review the main studies describing the effects of alcohol on different types of progenitor/stem cells including neuronal, hepatic, intestinal and adventitial progenitor cells, bone-marrow-derived stromal cell, dental pulp, embryonic and hematopoietic stem cells, and tumor-initiating cells. A better understanding of the nature of the cellular damage induced by chronic and episodic heavy (binge) drinking is critical for the improvement of current therapeutic strategies designed to treat patients suffering from alcohol-related disorders.

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Epigenetic mediators and consequences of excessive alcohol consumption

Cited by 31 publications

References 77 publications

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

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

DNA methylation-independent growth restriction and altered developmental programming in a mouse model of preconception male alcohol exposure

Stem cells under the influence of alcohol: effects of ethanol consumption on stem/progenitor cells

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