Generation of the Early-Gestational Maternal Immune Activation Mouse Model to Assess Prenatal Inflammation on Neurodevelopment.

Abstract

Neurodevelopmental disorders (NDDs) arise from complex interactions between genetic and environmental risk factors, including prenatal immune activation. Maternal immune activation (MIA) in mice is a widely used model to study environmental contributions to NDDs; variability in experimental outcomes limits reproducibility. Here, we present a standardized protocol for inducing MIA during early gestation at embryonic day 9.5 (E9.5) in mice, incorporating multiple quality control metrics to assess immune response and predict pregnancy outcomes. Following administration of polyinosinic:polycytidylic acid (poly(I:C)), maternal serum cytokines are quantified to confirm robust immune activation, allowing an exclusion metric for low responders. Maternal weight trajectories from E0.5 to E12.5 are predictive of litter viability, with dams that produced litter exhibiting characteristic weight-gain patterns distinct from dams that lost a litter. We also observed that the animal vendor significantly influenced maternal immune response and litter viability, while poly(I:C) formulation was not a significant factor. Altogether, the protocol provides strategies to enhance the reproducibility of the early-gestational MIA model and the viability of the offspring by monitoring maternal immune response and weight changes, and by controlling animal vendors, to ultimately study the effect of prenatal immune activation on neurodevelopment.