Prenatal and postnatal effects of gestational immune activation on synaptic and neurodevelopmental pathways via epigenetic mechanisms (ChIP-seq)

Previous epidemiological research suggests that maternal immune activation (MIA) during early pregnancy is a significant risk factor for neurodevelopmental and psychiatric disorders in offspring. Epigenetic factors and chromatin-related phenomena remain largely plastic during the course of prenatal and early postnatal development, allowing a dynamic impact of environmental effects on access to genes and regulatory elements. In this study, we tested the effects of maternal infection with the mouse-adapted influenza A/WSN/33 (H1N1) virus as a MIA model. Additionally, to assess the prenatal and postnatal effects of MIA, we cross-fostered half of the neonatal mice immediately after birth.This study includes RNA-seq and ChIP-seq profiling (H3K27ac, H3K4me3) from the prefrontal cortex of MIA-exposed and control mice. RNA-seq and ChIP-seq data are submitted under separate Series and linked via sample annotations. Overall design: This study examined transcriptomic and epigenomic changes in offspring following maternal immune activation (MIA) via prenatal influenza infection. Timed pregnant CD1 mice were intranasally infected with 5 × 10³ pfu of influenza A/WSN/33 (H1N1) or mock-treated on embryonic day 9.5. At birth, ~50% of pups were cross-fostered to surrogate dams (MIA or control) to separate prenatal and postnatal influences. Offspring were weaned at P21, housed by sex, and assigned to one of seven groups based on birth and rearing conditions: Group A (Mock-Mock): Offspring born to control mother and raised by their birth mother, together with stepsiblings born to MIA-exposed mother. Group B (MIA-Mock): Offspring born to MIA-exposed mother but raised by control surrogate mother, together with stepsiblings born to this control mother. Group C (Mock-MIA): Offspring born to control mother but raised by MIA-exposed surrogate mother, together with stepsiblings born to this MIA mother. Group D (MIA-MIA): Offspring born to MIA-exposed mother and raised by their birth mother, together with stepsiblings born to control mother. Group E (Mock-Mock_1): Offspring born to control mother and raised by their birth mother, together with stepsiblings born to a different control mother. Group F (Mock-Mock_2): Offspring born to control mother but raised by control surrogate mother, together with stepsiblings born to the control surrogate mother. Group G (Mock-Mock_3): Offspring born to control mother and raised by their birth mother with no stepsiblings. Mice were sacrificed in adulthood. Frontal cortex (bregma 1.90–1.40) was collected for MOWChIP-seq profiling of H3K4me3 and H3K27ac. Neuronal nuclei were isolated via FACS (NeuN?), with ~10,000 nuclei used per ChIP replicate. Libraries were prepared using Accel-NGS 2S Plus and sequenced on an Illumina HiSeq 4000 (single-end, 50 bp), yielding ~15 million reads per sample.