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

Maternal dietary protein deficiency and gastrointestinal 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 2×2 design with two levels of dietary protein (24% versus 6%) and two levels of infection (repeated sham versus 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 the edgeR package using NetworkAnalyst. In response to maternal H. bakeri infection, 96 genes (88 up-regulated and eight down-regulated) were differentially expressed in the fetal brain. Differentially expressed genes were involved in metabolic processes, developmental processes and the immune system according to the PANTHER classification system. Among the important biological functions identified, several up-regulated genes have known neurological functions including neuro-development (Gdf15, Ing4), neural differentiation (miRNA let-7), synaptic plasticity (via suppression of NF-κß), neuro-inflammation (S100A8, S100A9) and glucose metabolism (Tnnt1, Atf3). However, in response to maternal protein deficiency, brain-specific serine protease (Prss22) was the only up-regulated gene and only one gene (Dynlt1a) responded to the interaction of maternal nematode infection and protein deficiency. In conclusion, maternal exposure to GI nematode infection from day 5 to 18 of pregnancy may influence developmental programming of the fetal brain.

Effects of a protein-free diet on worm recovery, growth, and distribution of Echinostoma caproni in ICR mice.

The effects of a protein-free diet on the host-parasite relationship of Echinostoma caproni in ICR mice were studied. The experimental diet was a customized protein-free diet (PFD) in pellet form containing 0% protein. The control diet consisted of a standard laboratory diet containing 23% casein as a source of protein. A total of 24 mice were each infected with 15 metacercarial cysts of E. caproni. Twelve mice were placed on the experimental diet (experimentals) and the remaining mice (controls) were placed on the control diet. Experimental and control mice were necropsied at 2, 3, and 4 weeks postinfection (p.i.). The weight of mice on the PFD was markedly lower than that of mice on the control diet. The length and circumference of the small intestine of infected mice on the PFD were significantly lower than those of the controls at 3 weeks p.i. (Student's t-test; P < 0.05). Worm recoveries from mice on the PFD were significantly lower than those of the controls at 3 weeks p.i. There was a significant decline in worm body area in worms from the mice on the PFD compared with those on the control diet at 2, 3, and 4 weeks p.i. Worm dry weights from mice on the PFD were significantly lower than those on the control diet at 2 weeks p.i. Worms from hosts on the PFD were located more posteriad in the gut than those recovered from mice on the control diet. The findings suggest that the PFD contributes to growth retardation of E. caproni in ICR mice.