The impact of paternal alcohol consumption on offspring brain and behavioral development.
BACKGROUND
Fetal 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 ethanol exposure, or PrEE, are apparent, the effects of preconception paternal ethanol 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 if PatEE impacts the development of the neocortex and behavior in offspring as demonstrated in maternal consumption models of FASD (El Shawa et al., 2013).


METHODS
In 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.


RESULTS
PatEE resulted in significant impact on neocortical development, including abnormal patterns of gene expression within the neocortex at P0, as well as subtle alterations in patterns of intraneocortical connections. Additionally, PatEE mice exhibited a sex-specific increase in activity and sensorimotor integration deficits at P20, as well as decreased balance, coordination, and short-term motor learning at P30. This suggests that PatEE may generate long-lasting, sex-specific effects on offspring behavior.


CONCLUSIONS
These 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.