Alcohol
tijdens de zwangerschap verandert mogelijk genen van baby*
Volgens een Australische studie, weliswaar met muizen blijkt dat als tijdens de zwangerschap alcohol
genuttigd wordt verschillende genen aan of uitgezet kunnen worden bij de foetussen.
Alle mannetjes die deelnamen aan het experiment hadden twee exemplaren van een gen voor een bruine vacht. De vrouwtjes,
die elke dag tijdens de zwagerschap alcohol te drinken kregen, waren drager van twee genen voor een geelachtige vacht.
Dit zou normaal gesproken leiden tot een voorspelbaar percentage van muizen met een bruine, gele en gemengde vacht.
Doch nu bleek dat de vrouwtjes twee keer zo veel bruine jongen op de wereld zetten als volgens de wetten van kansberekening mocht worden aangenomen.
Volgens de wetenschappers toont de onverwachte vachtkleur van de muizen aan dat drinken tijdens de zwangerschap kan leiden tot
epigenetische veranderingen in het DNA. Dit betekent dat alcohol het genoom van de muizen
beïnvloedde door bepaalde genen aan of uit te zetten, verklaart onderzoeksleidster Suyinn Chong.
Ze vermoedt dat bij mensen eenzelfde mechanisme optreedt als vrouwen alcohol drinken tijdens de zwangerschap.
De alcohol bleek overigens niet alleen van invloed op de vachtkleur van de muizen. Ook de expressie van vijftien genen in de levercellen van de jonge muizen bleken te zijn veranderd als gevolg van de drinkgewoontes van hun moeder.
Maternal Ethanol Consumption Alters the Epigenotype and the Phenotype of Offspring in a Mouse Model
Nina Kaminen-Ahola1, Arttu Ahola1,2, Murat Maga3, Kylie-Ann Mallitt1, Paul Fahey1, Timothy C. Cox3, Emma Whitelaw1,4, Suyinn Chong1,4*
1 Division of Genetics and Population Health, Queensland Institute of Medical Research, Herston, Australia, 2 Department of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland, 3 Division of Craniofacial Medicine, Department of Pediatrics, University of Washington, Seattle, Washington, United States of America, 4 Griffith Medical Research College, Griffith University and the Queensland Institute of Medical Research, Herston, Australia
Abstract
Recent studies have shown that exposure to some nutritional supplements and chemicals in utero can affect the epigenome of the developing mouse embryo, resulting in adult disease. Our hypothesis is that epigenetics is also involved in the gestational programming of adult phenotype by alcohol. We have developed a model of gestational ethanol exposure in the mouse based on maternal ad libitum ingestion of 10% (v/v) ethanol between gestational days 0.5–8.5 and observed changes in the expression of an epigenetically-sensitive allele, Agouti viable yellow (Avy), in the offspring. We found that exposure to ethanol increases the probability of transcriptional silencing at this locus, resulting in more mice with an agouti-colored coat. As expected, transcriptional silencing correlated with hypermethylation at Avy. This demonstrates, for the first time, that ethanol can affect adult phenotype by altering the epigenotype of the early embryo. Interestingly, we also detected postnatal growth restriction and craniofacial dysmorphology reminiscent of fetal alcohol syndrome, in congenic a/a siblings of the Avy mice. These findings suggest that moderate ethanol exposure in utero is capable of inducing changes in the expression of genes other than Avy, a conclusion supported by our genome-wide analysis of gene expression in these mice. In addition, offspring of female mice given free access to 10% (v/v) ethanol for four days per week for ten weeks prior to conception also showed increased transcriptional silencing of the Avy allele. Our work raises the possibility of a role for epigenetics in the etiology of fetal alcohol spectrum disorders, and it provides a mouse model that will be a useful resource in the continued efforts to understand the consequences of gestational alcohol exposure at the molecular level.
Author Summary
In humans it has been known for some time that exposure to environmental insults during pregnancy can harm a developing fetus and have life-long effects on the individual's health. A well known example is fetal alcohol syndrome, where the children of mothers that consume large amounts of alcohol during pregnancy exhibit growth retardation, changes to the shape and size of the skull, and central nervous system defects. At present the molecular events underlying fetal alcohol syndrome are unknown. We have developed a model of alcohol exposure in the mouse, in which the genetics and the environment can be strictly controlled. We find that chronic exposure of the fetus to a physiologically relevant amount of alcohol during the first half of pregnancy results in epigenetic changes at a sensitive reporter gene and produces fetal alcohol syndrome-like features in some mice. Our model is a useful tool to study the underlying causes of fetal alcohol syndrome, and our work raises the interesting possibility that the long-term physical effects of alcohol exposure during pregnancy are mediated by epigenetic changes established in the fetus and then faithfully remembered for a lifetime. In the future, such epigenetic changes could be used as markers for the preclinical diagnosis and treatment of fetal alcohol spectrum disorders.
Citation: Kaminen-Ahola N, Ahola A, Maga M, Mallitt K-A, Fahey P, et al. (2010) Maternal Ethanol Consumption Alters the Epigenotype and the Phenotype of Offspring in a Mouse Model. PLoS Genet 6(1): e1000811. doi:10.1371/journal.pgen.1000811
Editor: Jeannie T. Lee, Massachusetts General Hospital, Howard Hughes Medical Institute, United States of America
Copyright: © 2010 Kaminen-Ahola et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by an Australian Research Council (ARC) Discovery Project grant (DP0878192) to EW and SC. NKA received funding from the Sigrid Juselius Foundation, Academy of Finland, Finnish Alcohol Research Foundation, the Finnish Cultural Foundation and Arvo and Lea Ylppo Foundation. TCC was supported by the Seattle Childrens Hospital and the Murdoch Charitable Trust. EW is a National Health and Medical Research Council (NHMRC) Australia Fellow. Part of this work was done in conjunction with the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), which is funded by grants from the National Institute on Alcohol and Alcohol Abuse (NIAAA), U24 AA014811. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: suyinn.chong@qimr.edu.au (Januari 2010)
