Developmental programming of the mouse: effects of maternal protein restriction on organ weight, nephron number and dimensions and gene expression
Background: In rats, a low protein (8%) diet throughout pregnancy leads to offspring with reduced nephron endowment. It has been suggested that the reduction in glomeruli may be the underlying causative factor in the high arterial pressures and aberrant renal function also observed in these offspring. To date, it is unknown whether the mouse can also be developmentally programmed via maternal protein restriction. Therefore, in this study we determined the effects of maternal protein restriction on mouse morphometry, glomerular number and dimensions and gene expression, to determine its suitability as a model in which to further study the effects and mechanisms of developmental programming.
Methods: C57/Bl6/129sv mice were exposed to either a normal (20 % w/w) or low (8 % w/w) protein diet during gestation and postnatal life. At postnatal day 30, male and females were euthanised and major organ weights determined. Left kidneys were processed in glycolmethacrylate, for subsequent glomerular number estimation via the disector/fractionator principle and right kidneys were harvested for analysis of gene expression.
Results: Maternal protein restriction resulted in a 23 % nephron deficit in postnatal day 30 male mice. All organ weights except the brain were reduced when normalised to body weight in both sexes. Furthermore, gene expression studies revealed sex-specific differences.
Conclusion: Our study provides evidence that the mouse is indeed a suitable model in which to study developmental programming, via maternal protein restriction. A perinatal low protein diet alters offspring nephron number, organ weight and renal gene expression, revealing important sex differences.