Early Maternal Alcohol Consumption Alters Hippocampal DNA Methylation, Gene Expression and Volume in a Mouse Model

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http://hdl.handle.net/10138/156987

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Marjonen , H , Sierra , A , Nyman , A , Rogojin , V , Grohn , O , Linden , A-M , Hautaniemi , S & Kaminen-Ahola , N 2015 , ' Early Maternal Alcohol Consumption Alters Hippocampal DNA Methylation, Gene Expression and Volume in a Mouse Model ' , PLoS One , vol. 10 , no. 5 , 0124931 . https://doi.org/10.1371/journal.pone.0124931

Title: Early Maternal Alcohol Consumption Alters Hippocampal DNA Methylation, Gene Expression and Volume in a Mouse Model
Author: Marjonen, Heidi; Sierra, Alejandra; Nyman, Anna; Rogojin, Vladimir; Grohn, Olli; Linden, Anni-Maija; Hautaniemi, Sampsa; Kaminen-Ahola, Nina
Contributor: University of Helsinki, Department of Medical and Clinical Genetics
University of Helsinki, Research Programs Unit
University of Helsinki, Medicum
University of Helsinki, Medicum
University of Helsinki, Medicum
Date: 2015-05-13
Language: eng
Number of pages: 20
Belongs to series: PLoS One
ISSN: 1932-6203
URI: http://hdl.handle.net/10138/156987
Abstract: The adverse effects of alcohol consumption during pregnancy are known, but the molecular events that lead to the phenotypic characteristics are unclear. To unravel the molecular mechanisms, we have used a mouse model of gestational ethanol exposure, which is based on maternal ad libitum ingestion of 10% (v/v) ethanol for the first 8 days of gestation (GD 0.5-8.5). Early neurulation takes place by the end of this period, which is equivalent to the developmental stage early in the fourth week post-fertilization in human. During this exposure period, dynamic epigenetic reprogramming takes place and the embryo is vulnerable to the effects of environmental factors. Thus, we hypothesize that early ethanol exposure disrupts the epigenetic reprogramming of the embryo, which leads to alterations in gene regulation and life-long changes in brain structure and function. Genome-wide analysis of gene expression in the mouse hippocampus revealed altered expression of 23 genes and three miRNAs in ethanol-exposed, adolescent offspring at postnatal day (P) 28. We confirmed this result by using two other tissues, where three candidate genes are known to express actively. Interestingly, we found a similar trend of upregulated gene expression in bone marrow and main olfactory epithelium. In addition, we observed altered DNA methylation in the CpG islands upstream of the candidate genes in the hippocampus. Our MRI study revealed asymmetry of brain structures in ethanol-exposed adult offspring (P60): we detected ethanol-induced enlargement of the left hippocampus and decreased volume of the left olfactory bulb. Our study indicates that ethanol exposure in early gestation can cause changes in DNA methylation, gene expression, and brain structure of offspring. Furthermore, the results support our hypothesis of early epigenetic origin of alcohol-induced disorders: changes in gene regulation may have already taken place in embryonic stem cells and therefore can be seen in different tissue types later in life.
Subject: PRENATAL ETHANOL EXPOSURE
VOMERONASAL SENSORY NEURONS
INDUCED BRAIN ABNORMALITIES
LONG-TERM POTENTIATION
SPATIAL MEMORY
VOLUNTARY CONSUMPTION
MAMMALIAN DEVELOPMENT
SPECTRUM DISORDER
ACUTE INSULT
MICE
3111 Biomedicine
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