There is increasing evidence of vitamin D insufficiency in women of child-bearing age and their infants. This study examined the effect of maternal vitamin D deficiency on nephron endowment in rat offspring (n=7 per group). Sprague-Dawley dams were fed either a vitamin D deplete diet or a vitamin replete (control) diet prior to pregnancy, during pregnancy and throughout lactation. At 4 weeks of age the offspring were weaned and maintained on their respective diets until they were killed at 7 weeks. In the fixed right kidney, kidney volume, renal corpuscle volume and nephron number were stereologically determined. There was no difference between groups in body weight, kidney weight or kidney volume. There was a significant 20% increase in nephron number in kidneys of vitamin D deplete offspring (vitamin D deficient, 29,000+/-1,858, control, 23,330+/-1,828; P=0.04). This was accompanied by a significant decrease in renal corpuscle size in the vitamin D deplete group compared with the controls (6.125+/-0.576 x 10(-4) mm(3) and 8.178+/-0.247 x 10(-4) mm(3), respectively; P=0.03). We concluded that maternal vitamin D deficiency in rats appears to stimulate nephrogenesis. Whether this confers a renal functional advantage or not is unknown.
A reduced nephron complement at birth renders the kidney susceptible to renal disease in adulthood. Retinoic acid (RA; the active metabolite of vitamin A) is linked to nephrogenesis in vitro and in vivo. The aim of this study was to determine the effect of administration of retinoic acid in midgestation in rats on nephron endowment in offspring exposed to maternal protein restriction. Rats were fed either a normal-protein diet (NPD) or a low-protein diet (LPD) during pregnancy and lactation. Half of the dams in the LPD group were injected intraperitoneally with retinoic acid (20 mg/kg) during gestation at embryonic day 11.5. At 4 weeks of age, the offspring were anesthetized and perfusion-fixed, and nephron number estimated using unbiased stereological techniques. Body weight and kidney volume was significantly reduced in all LPD offspring. There was a significant 29% reduction in nephron number in the LPD group compared with the NPD offspring, whereas the number of nephrons in kidneys from the LPD + RA offspring was not significantly different compared with controls. In conclusion, administration of a single bolus dose of retinoic acid during midgestation restored nephron endowment to normal in offspring exposed to maternal protein restriction.
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