Exploring epigenetic modifications following maternal immune activation: a focus on cross-species translational potential.

Maternal infection during pregnancy has emerged from epidemiological research as a key factor in the risk for neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and schizophrenia (SZ). Animal models provide translational tools to explore mechanisms linking maternal infection with altered offspring neurodevelopment. Maternal immune activation (MIA) models have been used to systematically explore the associations between specific maternal cytokines, in vivo measures of offspring brain, behavior and immune system development, and ultimately, to identify cellular and molecular changes that underly aberrant offspring neurodevelopment. Emerging evidence from rodent MIA models suggests that prenatal immune challenge induces NDD-relevant phenotypes not only in directly exposed individuals but also their descendants, suggesting that the public health consequences of MIA may be exponentially greater than previously understood. Epigenetic mechanisms have emerged as a critical, but understudied, area of research in the MIA field. Although epigenomic mechanisms could explain long-lived lifetime and intergenerational effects associated with maternal infection, there are limitations in translating epigenetic findings from preclinical rodent MIA models to humans. Here, we summarize the preclinical rodent studies investigating the effects of MIA on the offspring epigenome and highlight the translational potential of emerging data from non-rodent MIA models.