Abstract
BackgroundFetal 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.MethodsPregnant 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.ResultsProtein 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.ConclusionsChanges in cholesterol transport may contribute to altered tissue development in the fetus and hence programme risk of disease in later life.Electronic supplementary materialThe online version of this article (doi:10.1186/s12263-016-0541-3) contains supplementary material, which is available to authorized users.
Highlights
Fetal exposure to a maternal low protein diet during rat pregnancy is associated with hypertension, renal dysfunction and metabolic disturbance in adult life
We previously showed that exposure of the developing rat fetus to maternal undernutrition up to day 13 gestation induced changes in renal morphology that may underpin the development of hypertension in later life [7]
It should be noted that Cubn has a role in the uptake of high-density. In this experiment, we tested the hypothesis that maternal protein restriction would impact upon gene expression in the day-13 rat placenta
Summary
Fetal exposure to a maternal low protein diet during rat pregnancy is associated with hypertension, renal dysfunction and metabolic disturbance in adult life. We previously showed that exposure of the developing rat fetus to maternal undernutrition (both protein restriction and iron deficiency) up to day 13 gestation (full-term is 22 days) induced changes in renal morphology that may underpin the development of hypertension in later life [7] These effects were associated with a number of changes in the expression of genes and proteins in the day 13 embryo, which were clustered around regulation of the cell cycle, the cytoskeleton and formation of clathrin vesicles [7, 8]. We hypothesised that the established but immature placenta would show differential patterns of gene expression in response to maternal protein restriction These patterns may give important clues as to how maternal nutrition at this stage of development may have long-term consequences for the fetus
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