Starr Lisa M, Koski Kristine G, Scott Marilyn E
Institute of Parasitology, McGill University (Macdonald Campus), Ste-Anne-de-Bellevue, Québec H9X 3V9, Canada; Centre for Host Parasite Interactions, McGill University (Macdonald Campus), Ste-Anne-de-Bellevue, Québec H9X 3V9, Canada.
School of Dietetics and Human Nutrition, McGill University (Macdonald Campus), Ste-Anne-de-Bellevue, Québec H9X 3V9, Canada; Centre for Host Parasite Interactions, McGill University (Macdonald Campus), Ste-Anne-de-Bellevue, Québec H9X 3V9, Canada.
Int J Parasitol. 2016 Feb;46(2):97-104. doi: 10.1016/j.ijpara.2015.09.004. Epub 2015 Oct 22.
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.
肠道线虫感染和膳食蛋白质缺乏在孕期很常见，并且在人类、家畜和实验动物中均已表明这两者会损害胎儿生长。胎盘与胎儿生长有关，但其在介导母体感染和蛋白质缺乏反应中的作用尚不清楚。我们使用微阵列来检验以下假设：母体肠道线虫感染和蛋白质缺乏会改变与胎儿生长相关的胎盘基因的表达。在妊娠第18天，从喂食蛋白质充足（24%）或蛋白质缺乏（6%）等能量饮食且未感染或感染巴氏赫勒线虫的CD-1小鼠获取胎盘。使用Affymetrix GeneChip 2.0 ST小鼠阵列（每组n = 3）分析基因表达。使用双向方差分析（P<0.02，变化倍数>1.25）鉴定差异表达基因，并使用DAVID软件进行通路分析。使用qPCR确认所选基因的表达变化。巴氏赫勒线虫感染下调了109个转录本，包括与氧化磷酸化相关的基因，并上调了214个转录本，包括参与ATP结合和造血的基因。造血基因的上调可能解释了先前报道的感染巴氏赫勒线虫小鼠胎盘质量增加的现象。蛋白质缺乏下调了141个注释转录本，包括参与细胞运动和内肽酶活性的基因，并上调了131个注释转录本，包括与造血相关的基因。检测到248个转录本存在统计学相互作用，包括几个在胎儿生长中具有已知功能的基因。值得注意的是，胰岛素受体底物1（Irs1）基因在感染的母鼠中表达较低，但仅在它们喂食蛋白质充足的饮食时如此。此外，包括胰岛素样生长因子1受体（Igf1r）和催乳素（Prl）在内的几个基因的表达在蛋白质缺乏的感染母鼠中因感染而上调，在未感染母鼠中因蛋白质缺乏而下调。我们的结果突出表明，参与胎儿生长的胎盘基因表达受蛋白质缺乏和巴氏赫勒线虫感染之间相互作用的影响。
