Expression of growth-related genes in the mouse placenta is influenced by interactions between intestinal nematode (Heligmosomoides bakeri) infection and dietary protein deficiency

Abstract

Intestinal nematode infection and dietary protein deficiency are common during pregnancy and both have been shown to impair fetal growth in humans, livestock and laboratory animals. The placenta has been linked to fetal growth but its role in mediating the response to maternal infection and protein deficiency is not understood. We used microarrays to test the hypothesis that maternal intestinal nematode infection and protein deficiency alter the expression of placental genes related to fetal growth. Placentas were obtained on day 18 of pregnancy from CD-1 mice fed protein sufficient (24%) or protein deficiency (6%) isoenergetic diets and either uninfected or infected with Heligmosomoides bakeri. Gene expression was analysed using the Affymetrix GeneChip 2.0 ST mouse array (n=3/experimental group). Differentially expressed genes were identified using two-way ANOVA (P<0.02, fold-change >1.25) and pathway analyses were performed using DAVID software. Expression changes for selected genes were confirmed using qPCR. Heligmosomoides bakeri infection down-regulated 109 transcripts, including genes related to oxidative phosphorylation, and up-regulated 214 transcripts, including genes involved in ATP binding and hemopoiesis. Up-regulation of hemopoiesis genes may explain increased placental mass previously reported in H. bakeri-infected mice. Protein deficiency down-regulated 141 annotated transcripts, including genes involved in cell motility and endopeptidase activity, and up-regulated 131 annotated transcripts, including genes related to hemopoiesis. A statistical interaction was detected for 248 transcripts, including several genes with known functions in fetal growth. Notably, expression of the gene Irs1 (insulin receptor substrate) was lower in infected dams but only when they were fed a protein sufficient diet. Also, expression of several genes, including Igf1r (insulin-like growth factor-1 receptor) and Prl (prolactin) was up-regulated by infection in protein deficiency dams and down-regulated by protein deficiency in uninfected dams. Our results highlight that expression of placental genes involved in fetal growth is influenced by the interaction between protein deficiency and H. bakeri infection.