Preconception stress in mice alters maternal behavioral, neural, and endocrine outcomes, and produces sex-specific disruptions in offspring

Abstract

Disruptions to maternal behaviors that emerge during the peripartum period have been shown to have lasting physiological and behavioral consequences for offspring. In addition to effects on offspring, disrupted maternal behaviors have been associated with peripartum mood and anxiety disorders. Therefore, it is critical for the wellbeing of both mother and offspring to identify upstream risk factors for the disruption of maternal behavior. We have previously found that pubertal stress leads to a blunted hypothalamic-pituitary-adrenal (HPA) axis response in peripartum humans and mice. Given that dysfunction of the HPA axis is associated with both PMADs and disrupted maternal behavior, we examined how pubertal stress influenced maternal behavior throughout peripartum in mice using a pup retrieval test. We found that pubertal stress led to faster pup retrieval, but a less predictable pattern of maternal behavior, as well as a blunted HPA axis response during pregnancy. We also examined whether maternal pubertal stress influenced offspring behavior in adolescence and adulthood. We found sex-specific differences in risk-taking behavior during adolescence that are no longer present in adulthood. Finally, we used in situ hybridization to examine gene expression during pregnancy in the medial preoptic area of the hypothalamus, a region implicated in maternal behavior. Following pubertal stress, we found cell-type specific changes in the expression of genes necessary for the expression of maternal behavior. Collectively, these findings contribute to our understanding of upstream risk factors for peripartum disruptions to maternal behavior and the lasting effects of pubertal stress on both mother and offspring.