Parental binge alcohol abuse alters F1 generation hypothalamic gene expression in the absence of direct fetal alcohol exposure

• Published in: PloS one 2014-02, Vol.9 (2), p.e89320
• Main Authors: Przybycien-Szymanska, Magdalena M, Rao, Yathindar S, Prins, Sarah A, Pak, Toni R
• Format: Article
• Language: English
• Subjects: Abuse; Alcohol abuse; Alcohol use; Alcoholic Intoxication - embryology; Alcoholic Intoxication - genetics; Alcoholic Intoxication - pathology; Alcoholism; Alcohols; Analysis; Animals; Binge Drinking - drug therapy; Binge Drinking - genetics; Binge Drinking - pathology; Biology; Biomarkers - metabolism; Body Weight; Brain; Brain research; Child development; Chromatin; Chromatin remodeling; DNA microarrays; Drinking water; Drug abuse; Epigenetic inheritance; Epigenetics; Ethanol; Ethanol - toxicity; Exposure; Families & family life; Female; Females; Fetal Alcohol Spectrum Disorders - drug therapy; Fetal Alcohol Spectrum Disorders - genetics; Fetal Alcohol Spectrum Disorders - pathology; Fetal alcohol syndrome; Fetal development; Gene expression; Gene Expression Profiling; Gene Expression Regulation - drug effects; Gene regulation; Genes; Genomes; Genomics; Gestation; Hypothalamus; Hypothalamus - drug effects; Hypothalamus - metabolism; Hypothalamus - pathology; Laboratories; Ligands; Male; Males; Mating; Medicine; MicroRNAs; Neurodevelopment; Neurogenesis; Offspring; Oligonucleotide Array Sequence Analysis; Parents; Physiology; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Prenatal Exposure Delayed Effects - genetics; Prenatal Exposure Delayed Effects - pathology; Progeny; Puberty; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Rodents; Stress; Stress response; Studies; Substance abuse treatment; Synaptic plasticity; Transcription; Transcription (Genetics); Twins; Weaning
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0089320

Adolescent binge alcohol exposure has long-lasting effects on the expression of hypothalamic genes that regulate the stress response, even in the absence of subsequent adult alcohol exposure. This suggests that alcohol can induce permanent gene expression changes, potentially through epigenetic modifications to specific genes. Epigenetic modifications can be transmitted to future generations therefore, and in these studies we investigated the effects of adolescent binge alcohol exposure on hypothalamic gene expression patterns in the F1 generation offspring. It has been well documented that maternal alcohol exposure during fetal development can have devastating neurological consequences. However, less is known about the consequences of maternal and/or paternal alcohol exposure outside of the gestational time frame. Here, we exposed adolescent male and female rats to a repeated binge EtOH exposure paradigm and then mated them in adulthood. Hypothalamic samples were taken from the offspring of these animals at postnatal day (PND) 7 and subjected to a genome-wide microarray analysis followed by qRT-PCR for selected genes. Importantly, the parents were not intoxicated at the time of mating and were not exposed to EtOH at any time during gestation therefore the offspring were never directly exposed to EtOH. Our results showed that the offspring of alcohol-exposed parents had significant differences compared to offspring from alcohol-naïve parents. Specifically, major differences were observed in the expression of genes that mediate neurogenesis and synaptic plasticity during neurodevelopment, genes important for directing chromatin remodeling, posttranslational modifications or transcription regulation, as well as genes involved in regulation of obesity and reproductive function. These data demonstrate that repeated binge alcohol exposure during pubertal development can potentially have detrimental effects on future offspring even in the absence of direct fetal alcohol exposure.