Poster abstracts
Poster number 37 submitted by Branden Verosky
Prenatal stress impairs placental immune function
Branden Verosky (Neuroscience Program, The Ohio State University), Helen Chen, Ph.D. (Medical Scientist Training Program, The Ohio State University), Tamar Gur, M.D., Ph.D (Department of Psychiatry & Behavioral Health, The Ohio State University)
Abstract:
Despite the increasing prevalence of Autism spectrum disorder (ASD) and schizophrenia, the etiology of these diseases is not understood, prohibiting the development of interventions. ASD and schizophrenia are hypothesized to have an overlap in their pathophysiology due to shared symptoms and associated environmental contributions to their development. Both disorders are associated with in utero exposure to maternal infection, stress, and cytokine levels, which has led to the hypothesis of maternal immune programming of these disorders. Mouse models of prenatal stress and maternal immune activation have both shown the offspring to display a similar behavioral phenotype to what is seen in these disorders. However, for these maternal changes to program the offspring they need to first interact with the placenta. To elucidate the role of the placenta in perturbing development following prenatal stress and maternal viral stimulation our lab utilizes a mouse model of prenatal stress and maternal exposure to the viral mimetic poly(I:C). First, pregnant dams underwent 2 hours of daily restraint stress from gestational day (GD) 10.5 to GD16.5 or were left undisturbed and placentas were collected on GD17.5 to undergo single cell RNA-sequencing. Another cohort of dams underwent the same stress paradigm but were injected with poly(I:C) or saline on GD16.5 and tissue was collected 3 hours later. Cytokines and gene expression were measured in the placenta, fetal brain, and plasma. Transcriptomics revealed that stress causes a decreased proportion of maternal macrophages in the placenta with immune cell populations having a decreased response to interferons. Further, prenatal stress impaired the maternal cytokine response to poly(I:C) and impaired interferon signaling in the placenta. These results suggest that prenatal stress promotes an immunosuppressive environment in the placenta through decreasing the number of maternal macrophages and impairing the interferon response.
Keywords: Prenatal Stress, Maternal Immune Activation, Placental Immunity