Abstract
Research suggests that exposure to stress during the early postpartum period impacts both the mother and her offspring. For the offspring, early life stress (ELS) is associated with increased risk of developing pathological disease in adulthood. ELS triggers the activation of the HPA axis, potentially resulting in dysregulation. The developing hypothalamic-pituitary-adrenal (HPA) axis is particularly vulnerable during this period. Studies have established links between ELS, HPA axis dysregulation, and increased susceptibility to neuropsychiatric disorders, including anxiety and depression. Exposure to postpartum stress can also impair maternal behaviour and lead to inconsistent care of the offspring, ultimately inducing more stress in the offspring.
This study employed a mouse model to determine the effects of ELS on maternal behaviour in mouse dams and anxiety behaviour and HPA axis function in the offspring. The ELS paradigm involved placing dams and their pups into cages with limited nesting and bedding material, as well as a mesh floor, from postnatal day 2 to 9. Daily weight measurements were taken during this period, revealing no differences between ELS and control dams but a significant reduction in body weight among ELS offspring. During this period, behavioural testing to assess maternal behaviour and anxiety was conducted on the dams, including climbing a barrier to retrieve pups, assessing pup retrieval in a novel T maze, and evaluating anxiety-like behaviour in an elevated plus maze. Barrier climb testing revealed altered and adverse maternal care, however, most behaviours observed during T maze testing remained consistent with the control group. However, one notable change was demonstrated with ELS mice spending significantly less time on the nest compared to the control. Additionally, elevated plus maze testing showed no differences in anxiety-like behaviours between ELS and control dams. Offspring corticosterone (CORT) levels were assessed using enzyme-linked immunosorbent assays. Young (PND10) mice that were exposed to ELS had a significantly elevated CORT level compared to control, however, this was not seen in adult (8-week-old) offspring. Additionally, adult offspring underwent behaviour testing to measure anxiety-like behaviours. Interestingly, male ELS offspring exhibited less anxiety-like behaviours in elevated plus maze testing when compared to the male control group. Some interactions were observed between ELS and sex in the distance travelled within the inner zone during open field testing. Finally, ELS mice had increased anxiety-like behaviour in light dark box testing, particularly in female offspring. The results of the anxiety testing in the offspring showed that exposure to ELS induced changes in anxiety behaviour that were different in males and females depending on the test used. Our study demonstrates that an ELS paradigm can prompt behavioural changes in offspring and mothers and elevate CORT levels and reduce weight in young offspring. These results provide insights into the impact of postpartum and childhood stress, particularly on behavioural outcomes.