title: The effect of maternal undernutrition on the rat placental transcriptome: protein restriction up-regulates cholesterol transport.
abstract: BACKGROUND
  Fetal exposure to a maternal low protein diet during rat pregnancy is associated with hypertension, renal dysfunction and metabolic disturbance in adult life. These effects are present when dietary manipulations target only the first half of pregnancy. It was hypothesised that early gestation protein restriction would impact upon placental gene expression and that this may give clues to the mechanism which links maternal diet to later consequences.
  
  
  METHODS
  Pregnant rats were fed control or a low protein diet from conception to day 13 gestation. Placentas were collected and RNA sequencing performed using the Illumina platform.
  
  
  RESULTS
  Protein restriction down-regulated 67 genes and up-regulated 24 genes in the placenta. Ingenuity pathway analysis showed significant enrichment in pathways related to cholesterol and lipoprotein transport and metabolism, including atherosclerosis signalling, clathrin-mediated endocytosis, LXR/RXR and FXR/RXR activation. Genes at the centre of these processes included the apolipoproteins ApoB, ApoA2 and ApoC2, microsomal triglyceride transfer protein (Mttp), the clathrin-endocytosis receptor cubilin, the transcription factor retinol binding protein 4 (Rbp4) and transerythrin (Ttr; a retinol and thyroid hormone transporter). Real-time PCR measurements largely confirmed the findings of RNASeq and indicated that the impact of protein restriction was often striking (cubilin up-regulated 32-fold, apoC2 up-regulated 17.6-fold). The findings show that gene expression in specific pathways is modulated by maternal protein restriction in the day-13 rat placenta.
  
  
  CONCLUSIONS
  Changes in cholesterol transport may contribute to altered tissue development in the fetus and hence programme risk of disease in later life.
authors: School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, LE12 5RD UK.
authors: Zoe
authors: Z
authors: Daniel
authors: School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, LE12 5RD UK.
authors: Angelina
authors: A
authors: Swali
authors: School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Loughborough, UK ; Advanced Data Analysis Centre, University of Nottingham, Sutton Bonington, Loughborough, UK.
authors: Richard
authors: R
authors: Emes
authors: School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, LE12 5RD UK.
authors: Simon C
authors: SC
authors: Langley-Evans
keywords: Cholesterol; Placenta; Pregnancy; Protein restriction; Transcriptome; Undernutrition