Sex differences in the vulnerability of the hippocampus to prenatal stress

Abstract

Distressing events during pregnancy that engage activity of the body's endocrine stress response have been linked with later life cognitive deficits in offspring and associated with developmental changes in cognitive-controlling neural regions. Interestingly, prenatal stress (PS)-induced alterations have shown some sex specificity.Here, we review the literature of animal studies examining sex-specific effect of physical PS on the function and structure of the hippocampus as hippocampal impairments likely underlie PS-associated deficits in learning and memory. Furthermore, the connectivity between the hypothalamic-pituitary-adrenal (HPA) axis and the hippocampus as well as the heavy presence of glucocorticoid receptors (GRs) in the hippocampus suggests this structure plays an important role in modulation of activity within stress circuitry in a sex-specific pattern. We hope that better understanding of sex-specific, PS-related hippocampal impairment will assist in uncovering the molecular mechanisms behind sex-based risk factors in PS populations across development, and perhaps contribute to greater precision in management of cognitive disturbances in this vulnerable population.

Association of cumulative prenatal adversity with infant subcortical structure volumes and child problem behavior and its moderation by a coexpression polygenic risk score of the serotonin system

“…Analyzing GxE effects on infant subcortical structure volumes, we only observed a sex-specific GxE effect on right hippocampal volumes. In rats, sex differences in gene expression in the hippocampus have been reported (Yagi & Galea, 2019), and prenatal stress has been shown to affect the serotonergic network in the animal hippocampus, likely independent of sex (Soti et al, 2022). As our GxExSex analyses lacked power due to the small sample size, our results have to be considered as very tentative and future studies with larger samples are warranted for replication.…”

Gender medicine and sleep disorders: from basic science to clinical research

“…Additional basic research seeks to determine if there are gender disparities in sleep-related breathing disorders in adults as a result of perinatal exposure to different types of stress (chemical, behavioral, and social). This line of research has become increasingly relevant as awareness has emerged that the impacts of perinatal stress vary by gender ( 11 ), and that these impacts are particularly significant on the hippocampus ( 12 ), a brain region which plays a central role in mediating the long-term effects of stress ( 13 ). Recent unpublished preliminary data indicates that females may be more sensitive than males to perinatal exposure to chlorpyriphos, an organophosphate pesticide, leading to a higher prevalence of sleep apneas in adulthood [Bologna PRISM Lab ongoing studies by Berteotti et al ( 14 )].…”