Associate Professor University of Western Ontario London, Ontario, Canada
Abstract Authors: Stephen J. Renaud
Department of Anatomy and Cell Biology, University of Western Ontario, London, Canada Children's Health Research Institute, London, Canada
Abstract Text: Maternal immune activation (MIA) is a prenatal risk factor in which maternal immune responses during pregnancy can disrupt fetal development, particularly brain development, leading to lasting neurodevelopmental consequences. In rodent models, MIA is commonly induced using the viral mimetic PolyI:C, which results in sex-specific behavioral changes in offspring that resemble features of human neurodevelopmental disorders. As the interface between mother and fetus, the placenta plays a critical role in shaping fetal brain development. However, placental responses to MIA and their consequences for the fetal brain remain poorly understood. To investigate this, we injected pregnant rats with PolyI:C or saline at various gestational timepoints and performed RNA sequencing to assess acute placental responses. We also examined neural precursor cell function from MIA-exposed fetuses, and evaluated long-term behavioral changes in offspring. Maternal PolyI:C administration was associated with reduced fetal weight and persistent behavioral alterations in offspring. Neural precursor cells from PolyI:C-exposed fetuses exhibited increased proliferative capacity. Transcriptomic analysis revealed substantial changes in placental gene expression following MIA, including altered expression of genes involved in nervous system development and endocrine signaling. Notably, female placentas displayed a more robust response to MIA than male placentas, which may underlie sex-specific outcomes in MIA-exposed offspring.
