Binge Drinking and Intergenerational Implications: Parental Preconception Alcohol Impacts Offspring Development in Rats

Abstract

Preconception behaviors and experiences of mothers and fathers can affect future offspring. Recently, our laboratory showed that alcohol-naive offspring of parents who were exposed to repeated binge alcohol during adolescence showed altered DNA methylation patterns in the hypothalamus, a brain region involved in regulation of pubertal development, stress, and behavior. These observations have potentially far-reaching consequences for human health, as more than 4.6 million Americans under the age of 21 years report engaging in the rapid intoxication behavior of binge-pattern alcohol (EtOH) drinking. Therefore, we tested the hypothesis that offspring of binge EtOH‒exposed parents would have altered hypothalamic function manifested phenotypically as improper pubertal development, impaired socialization, and dysregulated stress response. In addition, we tested the hypothesis that parental EtOH exposure would confer adaptive protection from the negative effects of EtOH when offspring were themselves exposed to EtOH. Rats received EtOH via oral gavage once daily for 6 days at both early [postnatal day (PND) 37] and late puberty (PND 67). Animals were paired (EtOH-EtOH, vehicle-vehicle) for mating 24 hours after the last EtOH dose. After weaning, offspring were randomized to vehicle treatment to assess changes in normal development or to EtOH treatment to assess the effect of parental EtOH exposure on offspring response to this treatment. We found that offspring had smaller body weights and displayed fewer play behaviors when parents had been exposed to EtOH before conception. In addition, offspring showed a reduction in pubertal development markers that could indicate that parental preconception EtOH exposure confers maladaptive epigenetic traits in first-generation offspring.