The Impact of Paternal Alcohol Consumption on Offspring Brain and Behavioral Development

Abstract

BackgroundFetal alcohol spectrum disorders (FASD) describe the wide array of long‐lasting developmental abnormalities in offspring due to prenatal alcohol (ethanol [EtOH]) exposure via maternal gestational drinking. Although the teratogenic consequences of prenatal EtOH exposure, are apparent, the effects of preconception paternal EtOH exposure (PatEE) are still unclear. Previous research suggests that PatEE can induce molecular changes and abnormal behavior in the offspring. However, it is not known whether PatEE impacts the development of the neocortex and behavior in offspring as demonstrated in maternal consumption models of FASD (J Neurosci, 33, 2013, 18893).MethodsIn this study, we utilized a novel mouse model of PatEE where male mice self‐administered 25% EtOH for an extended period prior to conception, generating indirect exposure to the offspring through the paternal germline. Following mating, we examined the effects of PatEE on offspring neocortical development at postnatal day (P) 0 and evaluated several aspects of behavior at both P20 and P30 using a battery of behavioral assays.ResultsPatEE resulted in significant impact on neocortical development, including abnormal patterns of gene expression within the neocortex at P0 and subtle alterations in patterns of intraneocortical connections. Additionally, PatEE mice exhibited a sex‐specific increase in activity and sensorimotor integration deficits at P20, and decreased balance, coordination, and short‐term motor learning at P30. This suggests that PatEE may generate long‐lasting, sex‐specific effects on offspring behavior.ConclusionsThese results demonstrate that the developmental impact of preconception PatEE is more harmful than previously thought and provide additional insights into the biological mechanisms that may underlie atypical behavior observed in children of alcoholic fathers.

Paternal exposure to exercise and/or caffeine and alcohol modify offspring behavioral and pathophysiological recovery from repetitive mild traumatic brain injury in adolescence

“…Although, this finding is inconsistent with research on paternal alcohol exposure that found no difference in male and a reduction in female offspring anxiety‐like behavior, 74 the present study utilized a binge‐drinking model of alcohol consumption while the previous study exposed animals to a consistent but chronic dose of alcohol. Furthermore, research has showed that paternal alcohol exposure can cause expression of attention‐deficit/hyperactivity disorder (ADHD)‐like phenotypes 61,71 . Our study corroborates previous findings of ADHD‐like phenotypes in male offspring but also included female offspring and found similar phenotypes 61,71 .…”

“…To our knowledge paternal caffeine has never been studied, however prenatal maternal caffeine exposure induces both hyperactivity 68,69 and hypoactivity 70 in adolescent offspring. In addition, paternal alcohol exposure has been shown to induce hyperactive phenotypes in offspring 61,71 . While offspring hyperactivity was dependent on paternal drug treatment, offspring anxiety‐like phenotypes were sexually dimorphic and dependent on paternal experience.…”

Effects of Paternal Preconception Vapor Alcohol Exposure Paradigms on Behavioral Responses in Offspring

“…We found that all offspring, regardless of paternal ethanol exposure treatment, showed normal social behavior by preferring a social stimulus over an object. Recently, one study reported that paternal binge-like ethanol consumption had no effects on sociability in offspring [ 55 ], while another study showed antisocial behavior such as aggression in alcohol-sired male offspring [ 56 ]. Therefore, we assessed aggressive and defensive responses in offspring using the bottle-brush test, wherein there were no differences from controls observed in E-sired offspring.…”

Fetal alcohol spectrum disorders: Genetic and epigenetic mechanisms

“…Although FASD research has been mainly focused on the gestational period and maternal environmental factors during the pregnancy, also the impact of preconceptional—specifically paternal environment before fertilization—has been recognized. Paternal alcohol consumption can decrease the methylation level in human sperm 75 and paternal alcohol exposure has been associated with offspring's restricted growth, congenital anomalies and cognitive impairment in animal studies 76‐79 . The mechanism how paternal environmental exposures can affect the offspring's development is not yet known, but it seems that micro RNAs could explain how the alcohol‐induced effects can be transferred to the next generation 80,81 …”