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

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.

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Prenatal alcohol exposure is a leading cause of interneuronopathy in humans

Acta Neuropathologica Communications ◽

10.1186/s40478-020-01089-z ◽

2020 ◽

Vol 8 (1) ◽

Author(s):

Florent Marguet ◽

Gaëlle Friocourt ◽

Mélanie Brosolo ◽

Fanny Sauvestre ◽

Pascale Marcorelles ◽

...

Keyword(s):

Prenatal Alcohol Exposure ◽

Alcohol Exposure ◽

In Vitro Models ◽

Cortical Plate ◽

Gabaergic Interneurons ◽

Cortical Density ◽

Deep Layers ◽

Prenatal Alcohol ◽

Ganglionic Eminences

AbstractAlcohol affects multiple neurotransmitter systems, notably the GABAergic system and has been recognised for a long time as particularly damaging during critical stages of brain development. Nevertheless, data from the literature are most often derived from animal or in vitro models. In order to study the production, migration and cortical density disturbances of GABAergic interneurons upon prenatal alcohol exposure, we performed immunohistochemical studies by means of the proliferation marker Ki67, GABA and calretinin antibodies in the frontal cortical plate of 17 foetal and infant brains antenatally exposed to alcohol, aged 15 weeks’ gestation to 22 postnatal months and in the ganglionic eminences and the subventricular zone of the dorsal telencephalon until their regression, i.e., 34 weeks’ gestation. Results were compared with those obtained in 17 control brains aged 14 weeks of gestation to 35 postnatal months. We also focused on interneuron vascular migration along the cortical microvessels by confocal microscopy with double immunolabellings using Glut1, GABA and calretinin. Semi-quantitative and quantitative analyses of GABAergic and calretininergic interneuron density allowed us to identify an insufficient and delayed production of GABAergic interneurons in the ganglionic eminences during the two first trimesters of the pregnancy and a delayed incorporation into the laminar structures of the frontal cortex. Moreover, a mispositioning of GABAergic and calretininergic interneurons persisted throughout the foetal life, these cells being located in the deep layers instead of the superficial layers II and III. Moreover, vascular migration of calretininergic interneurons within the cortical plate was impaired, as reflected by low numbers of interneurons observed close to the cortical perforating vessel walls that may in part explain their abnormal intracortical distribution. Our results are globally concordant with those previously obtained in mouse models, in which alcohol has been shown to induce an interneuronopathy by affecting interneuron density and positioning within the cortical plate, and which could account for the neurological disabilities observed in children with foetal alcohol disorder spectrum.

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Prenatal Exposure to Alcohol, Tobacco, and Coffee: Associated Congenital Complications and Adverse Birth Outcomes

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18063140 ◽

2021 ◽

Vol 18 (6) ◽

pp. 3140

Author(s):

Sarah Soyeon Oh ◽

Sunwha Park ◽

Young-Ah You ◽

Yongho Jee ◽

AbuZar Ansari ◽

...

Keyword(s):

Birth Outcomes ◽

Prenatal Exposure ◽

Metabolic Diseases ◽

Prenatal Alcohol Exposure ◽

Coffee Consumption ◽

Alcohol Exposure ◽

Adverse Birth Outcomes ◽

South Korean ◽

Increased Risk ◽

Prenatal Alcohol

A few studies to date have examined the association between prenatal exposure to alcohol, tobacco, and coffee, and congenital complications/adverse birth outcomes among South Korean populations. Thus, this study analyzed the data of 1675 Korean women with birth experience within the last 3 years for pregnancy-related health and nutritional behaviors and relative outcomes. During their pregnancies, 11.58% of the study population consumed alcohol at least once, 1.43% drank throughout all three trimesters, 1.13% smoked, 25.43% were exposed to secondhand smoking, and 28.18% consumed 3 coffees or more every day. Prenatal alcohol exposure was associated with 11.24 times increased risk of birth defects/disabilities [Odds Ratio (OR): 11.24, 95% Confidence Interval (CI) 1.07–117.86] and 10.66 times increased risk of inherited metabolic diseases (OR: 10.66, 95% CI: 1.08–104.82). Prenatal secondhand smoke exposure (OR: 1.62, 95% CI: 1.01–2.62) and coffee consumption (OR: 1.92, 95% CI: 1.22–3.03) was associated with increased risk of low birth weight. Such results were in alignment with that of previous studies and confirmed that prenatal alcohol, tobacco, and coffee exposure can have detrimental neonatal and maternal consequences.

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Strengthening the Case: Prenatal Alcohol Exposure Is Associated With Increased Risk for Conduct Disorder

PEDIATRICS ◽

10.1542/peds.2008-1380 ◽

2008 ◽

Vol 122 (6) ◽

pp. e1225-e1230 ◽

Cited By ~ 67

Author(s):

E. R. Disney ◽

W. Iacono ◽

M. McGue ◽

E. Tully ◽

L. Legrand

Keyword(s):

Conduct Disorder ◽

Prenatal Alcohol Exposure ◽

Alcohol Exposure ◽

Increased Risk ◽

Prenatal Alcohol

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Fetal Cerebral Artery Mitochondrion as Target of Prenatal Alcohol Exposure

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16091586 ◽

2019 ◽

Vol 16 (9) ◽

pp. 1586 ◽

Cited By ~ 3

Author(s):

Anna N. Bukiya

Keyword(s):

Cerebral Artery ◽

Fetal Alcohol Spectrum Disorders ◽

Current Knowledge ◽

Prenatal Alcohol Exposure ◽

Specific Effect ◽

Alcohol Exposure ◽

Therapeutic Interventions ◽

Cellular Respiration ◽

Mitochondrial Morphology ◽

Prenatal Alcohol

Prenatal alcohol exposure results in an array of developmental abnormalities known as fetal alcohol spectrum disorders (FASDs). Despite the high prevalence of FASDs, therapeutic interventions against accidental or intended exposure of developing fetuses to alcohol are limited. This review outlines current knowledge about mitochondria in cerebral blood vessels as a potential target for anti-FASDs intervention. First, it describes the multifaceted role of mitochondria in maintaining the cerebral artery diameter as shown in adult tissue. Second, current literature on alcohol-driven damage of mitochondrial morphology and function in several fetal tissues, including liver, heart, and brain is summarized. The functional consequences of alcohol exposure in these organs include morphological enlargement of mitochondria, increased oxidative stress, and alteration of cellular respiration. These studies point to a tissue-specific effect of alcohol on mitochondrial function and a particular vulnerability of fetal mitochondria to alcohol exposure when compared to adult counterparts. Third, recent work from our group describing persistent changes in fetal baboon cerebral artery proteome following three episodes of prenatal alcohol exposure is reviewed. In conclusion, the consequences of prenatal alcohol exposure on cerebral artery mitochondria constitute an open field of investigation and, eventually, a point of therapeutic intervention against FASDs.

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Heavy prenatal alcohol exposure and increased risk of stillbirth

BJOG An International Journal of Obstetrics & Gynaecology ◽

10.1111/j.1471-0528.2012.03333.x ◽

2012 ◽

Vol 119 (8) ◽

pp. 945-952 ◽

Cited By ~ 18

Author(s):

C O’Leary ◽

P Jacoby ◽

H D’Antoine ◽

A Bartu ◽

C Bower

Keyword(s):

Prenatal Alcohol Exposure ◽

Alcohol Exposure ◽

Increased Risk ◽

Prenatal Alcohol

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Prenatal alcohol exposure affects developmental differentiation of interictal discharges in septal and temporal hippocampus

The International Journal of Developmental Biology ◽

10.1387/ijdb.210216cp ◽

2021 ◽

Author(s):

Maria-Eleni Evangelaki ◽

Caterina Psarropoulou

Keyword(s):

Prenatal Alcohol Exposure ◽

Hippocampal Slices ◽

Alcohol Exposure ◽

Receptor Activation ◽

Network Function ◽

Epileptiform Discharges ◽

Discharge Duration ◽

Prenatal Alcohol ◽

Interictal Discharges

Prenatal alcohol exposure (PAE) provokes lifelong CNS dysfunction, including an increased susceptibility to seizure disorders. We investigated hippocampal excitability in vitro in the offspring of dams exposed to a mild ethanol concentration throughout pregnancy (ethanol 15%v/v in drinking water). Hippocampal slices were prepared from the offspring at a Young (Y, 21-30 Postnatal Days, PND) or Adult (A, 60 PND) age, with controls from same age Normal rats (N). Synchronous spontaneous interictal-type epileptiform discharges (IEDs) were induced by bathing the slices in Mg2+-free ACSF or in 4-Aminopyridine (4-AP, 50µM) and were recorded from CA1 pyramidal layer of Temporal (T) and Septal slices (S). Hippocampal slices readily generated IEDs following NMDA receptor activation or K+ conductance block, with frequency and duration depending on location (septal or temporal), age, the activating mechanism, and prior conditioning (N or PAE). From the two media, 4-AP induced higher frequency (always), shorter duration (mostly) IEDs compared to Mg 2+-free ACSF. Temporal IED frequency increased with age, whereas Septal was stable, indicating an earlier maturation of the latter part. The hippocampal "T to S" (high to low) excitability gradient appeared at/later than the end of the first postnatal month and concerned mostly discharge frequency. Discharge duration generally decreased with maturation but appeared to depend on many factors including conditioning. Prenatal alcohol exposure differentiated the control of synchronous discharges by NMDA receptors and K+ conductances, and their developmental evolution, thus suggesting potential mechanisms for aberrant hippocampal neuronal network function.

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Prevalence of smoking during pregnancy in the Republic of the Congo: Maternal smoking is associated with increased risk of prenatal alcohol exposure

The International Journal of Alcohol and Drug Research ◽

10.7895/ijadr.v3i1.131 ◽

2014 ◽

Vol 3 (1) ◽

pp. 105-111 ◽

Cited By ~ 4

Author(s):

Andrew D. Williams ◽

Yannick Nkombo ◽

Gery Nkodia ◽

Gary Leonardson ◽

Larry Burd

Keyword(s):

Alcohol Use ◽

Maternal Smoking ◽

Prenatal Alcohol Exposure ◽

Alcohol Exposure ◽

Smoking During Pregnancy ◽

Maternal Alcohol ◽

Increased Risk ◽

Republic Of The Congo ◽

Prenatal Alcohol ◽

The Republic

Williams, A., Nkombo, Y., Nkodia, G., Leonardson, G., & Burd, L. (2014). Prevalence of smoking during pregnancy in the Republic of the Congo: Maternal smoking is associated with increased risk of prenatal alcohol exposure. The International Journal Of Alcohol And Drug Research, 3(1), 105-111. doi:10.7895/ijadr.v3i1.131Aims: Development of useful estimates of rates of maternal smoking during pregnancy, and the impact of smoking on rates and duration of maternal alcohol use during pregnancy.Design: A prospective study utilizing systematic screening of consecutive pregnant women.Setting: Ten prenatal care sites in Brazzaville, Congo’s largest city, where 50% of live births in the Congo occur. Women were asked to report the number of cigarettes smoked per day.Findings: From the 10 sites, 3,099 women were screened and 5.5% (n = 172) reported smoking. The mean number of cigarettes smoked per day was 1.1 and only 11% (n = 19) of the women reported smoking two or more cigarettes per day during pregnancy. Smoking during pregnancy was associated with a 4.9-fold increase in prenatal alcohol exposure during pregnancy. We found that 93% of the women who smoked also used alcohol during pregnancy.Conclusions: While the prevalence of smoking and the average number of cigarettes smoked per day were both low, smoking at any level results in a huge increase in risk for maternal alcohol use during pregnancy. The trend across the developing world is for increasing rates of smoking among women and children. Since the number of cigarettes smoked per day was low, smoking cessation programs and public health warnings may be useful in further reducing rates of smoking during pregnancy and, thus, risk for prenatal alcohol exposure in the Congo. We believe this is the first report quantifying the risk of smoking and prenatal alcohol use in a population of pregnant women.

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Complex Trauma and Prenatal Alcohol Exposure: Clinical Implications

Perspectives on School-Based Issues ◽

10.1044/sbi13.2.32 ◽

2012 ◽

Vol 13 (2) ◽

pp. 32-42 ◽

Cited By ~ 8

Author(s):

Yvette D. Hyter

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Child Development ◽

Academic Outcomes ◽

Complex Trauma ◽

Prenatal Alcohol Exposure ◽

Alcohol Exposure ◽

Clinical Implications ◽

Prenatal Alcohol ◽

The Brain

Abstract Complex trauma resulting from chronic maltreatment and prenatal alcohol exposure can significantly affect child development and academic outcomes. Children with histories of maltreatment and those with prenatal alcohol exposure exhibit remarkably similar central nervous system impairments. In this article, I will review the effects of each on the brain and discuss clinical implications for these populations of children.

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