Differential expression of genes in fetal brain as a consequence of maternal protein deficiency and nematode infection. Mus musculus

Maternal dietary protein deficiency and nematode infection during early pregnancy have negative impacts on both maternal placental gene expression and fetal growth in the mouse. Here we used next-generation RNA sequencing to test our hypothesis that maternal protein deficiency and/or nematode infection also alter the expression of genes in the developing fetal brain. Outbred pregnant CD1 mice were used in a 2x2 design with two levels of dietary protein (24% and 6%) and two levels of infection (repeated sham and Heligmosomoides bakeri beginning at gestation day 5). Pregnant dams were euthanized on gestation day 18 to harvest the whole fetal brain. Four fetal brains from each treatment group were analyzed using RNA Hi-seq sequencing and the differential expression of genes was determined by edgeR package using NetworkAnalyst. In response to maternal H. bakeri infection, 96 genes (88 up-regulated and 8 down-regulated) were differentially expressed in the fetal brain. Differentially expressed genes were involved in metabolic processes, developmental processes and immune system according to the PANTHER classification system. Among the important biological functions identified, several upregulated genes have known neurological functions including neurodevelopment (Gdf15, Ing4), neural differentiation (miRNA let-7), synaptic plasticity (via suppression of NF-κβ), neuro-inflammation (S100A8, S100A9) and glucose metabolism (Tnnt1, Atf3). However, in response to maternal protein deficiency, brain specific serine protease (Prss22) was the only upregulated gene and only one gene (Dynlt1a dynein light chain) responded to the interaction of maternal nematode infection and PD. In conclusion, maternal exposure to GI nematode infection from day 5 to 18 of pregnancy may influence developmental programming of the fetal brain. Overall design: 2 X 2 factorial design with two types of dietary protein and two levels of infection