Proceedings of The Physiological Society

University of Cambridge (2008) Proc Physiol Soc 11, C26

Oral Communications

Gene expression changes observed in the placenta from different maternal diets provide evidence for possible candidates for gatekeeper genes in development

A. Richmond1, L. Gambling1, C. Mayer2, S. C. Langley-Evans3, S. McMullen3, P. Taylor4, H. J. McArdle1

1. The Rowett Research Institute, Aberdeen, United Kingdom. 2. Biostatistics Scotland, The Rowett Research Institute, Aberdeen, United Kingdom. 3. University of Nottingham, Loughborough, United Kingdom. 4. King's College London, London, United Kingdom.

  • Figure 1: Gatekeeper hypothesis. Comparing the different stresses directly with each other identifies the commonly affected genes. The darkened central point contains these genes in common.

During pregnancy, the quality of diet a mother consumes is critical for the development of her fetus and a suboptimal diet can have deleterious consequences for the offspring, both short and long term. Studies have shown that a low protein, high fat or a low iron diet results in offspring that develop hypertension and obesity. This has lead to the Gatekeeper hypothesis, which suggests that diverse nutritional stresses affect common gene(s) or gene pathway(s), as detailed in Figure 1. We are using nutrigenomic approaches to identify these genes or gene pathways. All animal procedures were approved by the Home Office and methods used were compliant with the UK Animals (Scientific Procedures) Act, 1986. Day 21 gestational placentas from rats fed either a control, low protein, high fat or low iron diet during pregnancy were collected. RNA was prepared for micro array analysis on Affymetrix whole rat genome arrays. The data collected has undergone quality control and normalisation via the NuGO MadMax server. The resultant output produced includes unpaired t-test p-value and mean fold change. The data was then filtered according to p value of <0.05 and 20% fold change to determine differential gene expression. For each diet a number of genes showed significant changes. These included genes involved in growth regulation and DNA repair and metabolism and a number of ion and metal transporters. The data has identified several genes and gene pathways that are altered in common to the different diets and may be possible gatekeeper candidates. We are currently using pathway analysis tools to compare directly the different treatments and to test the gatekeeper theory. This approach has also provided evidence of gene expression changes in the placenta during different diet regimes. In addition, this methodology is also of excellent value, providing testable hypotheses for understanding the link between maternal diet and offspring health. This work was supported by RERAD and the EU (NuGO and EARNEST)

Where applicable, experiments conform with Society ethical requirements