Protein-energy malnutrition during early gestation in sheep blunts fetal renal vascular and nephron development and compromises adult renal function.

A nutritionally poor maternal diet can reduce nephron endowment and pre-empt premature expression of markers for chronic renal disease in the offspring. A mechanistic pathway from variation in maternal diet through altered fetal renal development to compromised adult kidney structure and function with adult-onset obesity has not been described. We show that maternal protein-energy malnutrition in sheep blunts nephrogenic potential in the 0.44 gestation (65 days gestation, term ∼147 days) fetus by increasing apoptosis and decreasing angiogenesis in the nephrogenic zone, effects that were more marked in male fetuses. As adults, the low-protein-exposed sheep had reduced glomerular number and microvascular rarefaction in their kidneys compensated for, respectively, by glomerular hypertrophy and increased angiogenic support. In this study, the long-term mild anatomical deficits in the kidney would have remained asymptomatic in the lean state, but when superimposed on the broad metabolic challenge that obesity represents then microalbuminuria and blunted bilateral renal function revealed a long-term physiological compromise, that is only predicted to worsen with age. In conclusion, maternal protein-energy malnutrition specifically impacts fetal kidney vascular development and prevents full functionality of the adult kidney being achieved; these residual deficits are predicted to significantly increase the expected incidence of chronic kidney disease in prenatally undernourished individuals especially when coupled with a Western obesogenic environment.

Developmental origins of obesity: programming of food intake or physical activity?

Mans ability to capture, harness and store energy most efficiently as fat in adipose tissue has been an evolutionary success story for the majority of human existence. Only over the last 30-40 years has our remarkable metabolic efficiency been revealed as our energy balance increasingly favours storage without regular periods of depletion. Historical records show us that while the composition of our diet has changed markedly over this time, our overall energy intake has significantly reduced. The inevitable conclusion therefore is that habitual physical activity and thus energy expenditure has reduced by a greater extent. Recent studies have illustrated how the finely tuned long-term control of energy intake and of energy expenditure are both developmentally plastic and susceptible to environmentally-induced change that may persist with that individual throughout their adult life, invariably rendering them more susceptible to greater adipose tissue deposition. The central role that lean body mass has upon the 'gating' of energy sensing and the importance of regular physical activity for its potential to reduce the burden of a 'thrifty phenotype' will be briefly discussed in the present review.

Maternal infection-induced white matter injury is reduced by treatment with interleukin-10.

OBJECTIVE: The purpose of this study was to test the hypothesis that interleukin-10 can prevent white matter injury in neonatal rats that are born to infected dams. STUDY DESIGN: Timed pregnant rats (day 17) were assigned to the following treatment groups: (1) saline control (n = 5 rats), (2) Escherichia coli- infected (n = 10 rats), and (3) E coli + interleukin-10 (n = 5 rats). E coli was administered at a titer of 1 x 10(7) colony-forming units by intrauterine inoculation just above the cervix at the bifurcation of the uterine horns. Rat interleukin-10 was administered intravenously at a dose of 1 microg/kg of body weight. After delivery, the pups were maintained with dams until day 8, at which time they were placed under general anesthesia and perfused with saline solution followed by 10% paraformaldehyde. The brains were removed, placed in 30% sucrose solution, and then frozen at -20 degrees C until the preparation of the frozen sections. Standard hematoxylin/eosin staining was performed, and the brains were evaluated for matter necrosis, apoptotic cells, and ventricular swelling. RESULTS: In pups that were born to infected dams, 11 of 38 pups (29%) displayed symmetric lesions around the lateral ventricles. These lesions were characterized by marked looseness/edema of the neuropil, foamy-appearing histiocytes, and granular neuropil breakdown. None of the pups (n = 17) that were born to interleukin-10-treated infected dams displayed this pattern of severe white matter injury. CONCLUSION: These results suggest that maternal interleukin-10 therapy could provide neuroprotection for infants who are born to mothers with intrauterine infection.