Effects of combined IUGR and prenatal stress on the development of the hippocampus in a fetal guinea pig model

Abstract

Intrauterine growth restriction (IUGR) and maternal stress during pregnancy are two compromises that negatively impact neurodevelopment and increase the risk of developing later life neuropsychiatric disorders such as schizophrenia, depression and behavioural disorders. Neurosteroids, particularly allopregnanolone, are important in protecting the developing brain and promoting many essential neurodevelopmental processes. Individually, IUGR and prenatal stress (PS) reduce myelination and neurogenesis within affected fetal brains, however less information is available on the combined effects of these two disorders on the term fetal brain. This study aimed to investigate how IUGR and PS impairs the neurosteroid pathway when combined using a guinea pig model, and how these then disrupt the neurodevelopment of the fetus. Uterine artery blood flow restriction was performed at GA30-35 to induce growth restriction, whilst PS was induced by exposure of the dam to a strobe light during gestation commencing GA40 and repeated every 5 days. Exposure in this model caused reductions in hippocampal CA1 MBP immunostaining of male fetuses in both IUGR alone and IUGR+PS paradigms but only by IUGR in the subcortical white mater, compared with control males. Plasma allopregnanolone was reduced by both stressors irrespective of sex, whereas GFAP or MAP2 expression were not affected by either stressor. Female neurodevelopment, as assessed by these markers, was unimpeded by these compromises. The addition of prenatal stress did not further compound these deficits.