Alcohol (ethanol [EtOH]) consumption during pregnancy is associated with altered offspring neurobehaviour and hypothalamus-pituitary-adrenal axis (HPA) function1. Although many cease alcohol upon pregnancy detection, 30% of women admit to drinking during the periconceptional period (PC)2. However, the impacts of EtOH exposure during PC on HPA outcomes is unknown. This study aimed to investigate the impacts of PC:EtOH exposure on rodent behavioural and HPA activity outcomes.
Sprague Dawley dams were treated with 12.5% ethanol or control liquid diet from 4 days before conception to embryonic day 4. Offspring were delivered naturally and at 3 months of age offspring underwent forced swim (FST) and social interaction (SI) tests followed by a dexamethasone suppression (DST), corticotropin hormone stimulation (CST) and restraint tests at 6 months of age. Further subsets of animals were culled for tissue collection for analysis of basal corticosterone and mRNA expression of HPA pathways at 6 and 15 months of age.
PC:EtOH resulted in increased immobility within the FST in offspring (p <0.05). There was an increase in social interaction (p <0.05) and elevated plasma corticosterone responses to the DST and CST in female offspring only (p <0.05). Interestingly, there was no significant PC:EtOH effect on corticosterone response during restraint test in either male or female offspring. Relative gene expression of the adrenal steroidogenic pathway (Mc2r, StAr, Cyp11a1, Hsd3ab, 11bhsd2, Cyp11a1, Nr3c1 and Hsp90) was not significantly different at 6 months of age, however hippocampal genes (Nr3c1 and Hsp90) were significantly elevated within female PC:EtOH offspring only at 15 months of age.
These results suggest that PC:EtOH alters behavioural outcomes and HPA reactivity within rodent offspring, with potential changes in the hippocampal regulation of the HPA axis of female offspring. Our results highlight that exposure to alcohol even before organogenesis and brain development can have significant adverse outcomes for offspring.