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Alcohol in pregnancy can affect multiple generations

Soon-to-be mothers have heard the warning - don't drink while pregnant. Despite this, many pregnant women do drink, a choice science has known for years can hurt the fetus. A new study now reveals more reason for restricting alcohol in pregnancy. Not only the current pregnancy but future generations can inherit brain malformation from that pregnancy's alchohol damaged chromosomes.


The Centers for Disease Control and Prevention (CDC) has issued numerous statements about the dangers of alcohol consumption during pregnancy, particularly as it can lead to Fetal Alcohol Spectrum Disorders (FASD) in newborns. Now, a new study by Kelly Huffman, assistant professor of psychology, at the University of California, Riverside, suggests chemical evidence of FASD may persist for multiple generations. The research was published in the journal Cerebral Cortex.
"Traditionally, prenatal ethanol exposure (PrEE) from maternal consumption of alcohol, was thought to solely impact directly exposed offspring, the embryo or fetus in the womb. However, we now have evidence that the effects of prenatal alcohol exposure could persist transgenerationally and negatively impact the next-generations of offspring who were never [directly] exposed to alcohol."

Kelly J. Huffman PhD, Assistant Professor, Department of Psychology, University of California at Riverside (UCR), California, USA.

Previous work from the Huffman Laboratory at UCR has shown PrEE impacts the anatomy of the neocortex, the part of the brain responsible for complex behavior and intellectual thought in humans. PrEE can also lead to abnormal motor behavior and increased anxiety in any exposed offspring. Huffman and her group now reveal that in utero alcohol exposure generates neurobiological and behavioral effects in multiple generations of mice without any alcohol exposure. This suggests chromosomal damage from alcohol drunken during pregnancy may be affecting germ cell development and inheritable.

To determine whether abnormalities in brain and behavior came from prenatal alcohol exposure, Huffman generated a mouse model of FASD and tested many aspects of brain and behavior development across just three generations. As expected, the first generation showed atypical gene formation, and therefore abnormal development of neural networks within the neocortex along with observable behavioral problems. However, the principal discovery came in the following, non-exposed generations of mice. These animals had neuro-developmental and behavioral problems similar to the first generation, the only directly exposed generation.
"We found that body weight and brain size were significantly reduced in all generations of PrEE animals when compared to controls [those pregnant mice unexposed to alcohol]. Also, all generations of PrEE mice showed increased anxiety, depressive behaviors and sensory-motor deficits. By demonstrating the strong transgenerational effects of prenatal ethanol exposure in a mouse model of FASD, we suggest that FASD may be a heritable condition in humans."

Kelly J. Huffman PhD

This study strongly suggests alcohol consumption while pregnant leads to a cascade of nervous system changes which appear to affect chromosome function in the developing fetus, and ultimately last over multimple generations. By gaining an understanding of these neurodevelopmental and behavioral effects, perhaps science through long term research, might develop novel therapies to address better outcomes. But immediately, mothers abstaining from drinking before attempting to get pregnant, and definitely during pregnancy, will benefit their children for generations.

Abstract
Fetal Alcohol Spectrum Disorders, or FASD, represent a range of adverse developmental conditions caused by prenatal ethanol exposure (PrEE) from maternal consumption of alcohol. PrEE induces neurobiological damage in the developing brain leading to cognitive-perceptual and behavioral deficits in the offspring. Alcohol-mediated alterations to epigenetic function may underlie PrEE-related brain dysfunction, with these changes potentially carried across generations to unexposed offspring. To determine the transgenerational impact of PrEE on neocortical development, we generated a mouse model of FASD and identified numerous stable phenotypes transmitted via the male germline to the unexposed third generation. These include alterations in ectopic intraneocortical connectivity, upregulation of neocortical Rzr? and Id2 expression accompanied by both promoter hypomethylation of these genes and decreased global DNA methylation levels. DNMT expression was also suppressed in newborn PrEE cortex, providing further insight into how ethanol perturbs DNA methylation leading to altered regulation of gene transcription. These PrEE-induced, transgenerational phenotypes may be responsible for cognitive, sensorimotor, and behavioral deficits seen in humans with FASD. Thus, understanding the possible epigenetic mechanisms by which these phenotypes are generated may reveal novel targets for therapeutic intervention of FASD and lead to advances in human health.

Keywords: alcohol, behavior, epigenetics, heritability, neocortex


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Jul 10, 2017   Fetal Timeline   Maternal Timeline   News   News Archive




Fetal Alcohol Spectrum Disorders, or FASD, presents as a range of developmental
brain, behavior and sometimes facial disorders, caused by prenatal ethanol
exposure (PrEE) from maternal consumption of alcohol.
Image Credit: Public domain



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