Impact of Maternal Immune Activation and Sex on Placental and Fetal Brain Cytokine and Gene Expression Profiles in a Preclinical Model of Neurodevelopmental Disorders

Maternal inflammation during gestation is associated with a later diagnosis of neurodevelopmental disorders including autism spectrum disorder (ASD). However, the specific impact of maternal immune activation (MIA) on placental and fetal brain development remains insufficiently understood. This study aimed to investigate the effects of MIA by analyzing placental and brain tissues obtained from the offspring of pregnant dams exposed to polyinosinic:polycytidylic acid (Poly I:C) on embryonic day 12.5. Cytokine and mRNA content in the placenta and brain tissues were assessed using multiplex cytokine assays and bulk-RNA sequencing on embryonic day 17.5. Bulk-RNA sequencing was performed on placenta and brain tissues on embryonic day 17.5. C57BL/6 mice were purchased from Taconic Biosciences. 8–10 week-old female C576B/L mice were paired with males. Insemination was confirmed by the presence of a vaginal plug the following morning, marking the gestational time as embryonic day (ED) 0.5. On embryonic day 12.5, pregnant dams were intraperitoneally administered 20mg/kg γ-irradiated Poly I:C (Sigma) to stimulate maternal immune activation. Control groups were administered saline. On ED17.5, fetal brains and placenta were collected and flash frozen and stored at -80 until cytokine and RNA analysis. To control for litter effect, 2 pups from each litter (1 male and 1 female) were used.