The effect of a maternal low protein diet on renal development and function in the offspring
Dunford, Louise Jane (2013) The effect of a maternal low protein diet on renal development and function in the offspring. PhD thesis, University of Nottingham.
A poor maternal diet leads to offspring with a greater risk of developing chronic diseases later in life. This thesis considered whether a low protein diet during pregnancy in sheep affected the development of the fetal kidney, and how this impacted upon adult renal function when challenged by obesity. Pregnant ewes were fed either a control diet or a diet that was isocaloric but contained only 50% of the protein, in either early or late gestation. The effects of the diet were assessed on the ewe, day 65 fetuses (0.44 gestation), and two year old offspring which had been subjected to an obesogenic environment (ab libitum feed and reduced exercise). Few effects were observed on the ewe, confirming that the nutritional insult was relatively mild. Fetal renal vasculature (assessed by vascular corrosion casts) was not different between groups, although the microvasculature was significantly reduced in the early protein group, as evidenced by CD34+ staining of endothelial cells. This was accompanied by a reduction in angiogenic factors compared to control animals. Protein-energy malnutrition in the ewe led to reduced urea in maternal and fetal plasma, along with a concomitant reduction in ornithine in the fetal plasma and amniotic fluid. Other amino acids were relatively unaffected. In the adult sheep there were no effects on long-term renal function in the group fed low protein late in pregnancy, despite the lambs having lower birth weights and a period of postnatal catch up growth compared to the other groups. However, the group fed low protein during early pregnancy had reduced nephron number, microalbumuria and reduced renal function as assessed by gamma scintigraphy. There was also evidence of microvascular rarefaction which may have been exacerbated by obesity. This study did not reveal any consistent sex-specific effects of the maternal low protein diet. This study emphasises the importance of diet quality rather than quantity, and the importance of consuming a well-balanced diet during pregnancy to protect against future chronic diseases.
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