Cell Cycle Regulation and Cytoskeletal Remodelling Are Critical Processes in the Nutritional Programming of Embryonic Development

Many mechanisms purport to explain how nutritional signals during early development are manifested as disease in the adult offspring. While these describe processes leading from nutritional insult to development of the actual pathology, the initial underlying cause of the programming effect remains elusive. To establish the primary drivers of programming, this study aimed to capture embryonic gene and protein changes in the whole embryo at the time of nutritional insult rather than downstream phenotypic effects. By using a cross-over design of two well established models of maternal protein and iron restriction we aimed to identify putative common “gatekeepers” which may drive nutritional programming

A low-protein isocaloric diet during gestation affects brain development and alters permanently cerebral cortex blood vessels in rat offspring

In humans, low birth weight is associated with nonfatal stroke, cardiovascular disease and diabetes at adulthood. The aim of this study was to investigate in rats the effect of early protein restriction, inducing low birth weight, on brain and endocrine pancreas vascularization at birth and to study if such alterations lasted until adulthood. Pregnant rats were fed either 20 or 8% protein isocaloric diets. Control newborns were nursed by their dams fed the 20% protein diet and low protein (LP) pups by dams fed either the 8 or 20% protein diet. The diets given during lactation were maintained until adulthood. The blood vessel density of cerebral cortex analyzed by morphometry in 3-d-old pups from dams fed the 8% protein diet was lower than in control (C). It remained lower at adulthood whether a LP or a C diet was given postnatally. Reduction of vascularization at adulthood induced by the LP diet limited to fetal life seems characteristic for the brain since vascularization of islets of Langerhans was reduced in neonates but normalized at adulthood by a C diet postnatally. Body and brain weights were lower in LP pups and adults. DNA concentration was lower in forebrain and higher in cerebellum in LP pups. In brain of LP adults, DNA, protein, cholesterol and phospholipid concentrations were tower and were restored at adulthood by a normal diet after birth. In conclusion, cerebral cortex of offspring exposed to a LP isocaloric diet during fetal development showed reduced vascularization which remained throughout life

Efeito do treinamento físico e da desnutrição durante a gestação sobre os eixos cranianos de ratos neonatos

Nos períodos críticos de desenvolvimento do organismo, estímulos ambientais como o exercício físico e a dieta podem influenciar o fluxo placentário e o crescimento somático fetal. O objetivo do presente estudo foi avaliar as repercussões do treinamento físico e da desnutrição durante a gestação sobre os eixos cranianos de ratos neonatos. Ratos machos Wistar foram divididos de acordo com a manipulação de suas mães: não treinados controle (Cf, n = 25), treinados (Tf, n = 25), não treinados e desnutridos (Df, n = 25), treinados e desnutridos (TDf, n = 25). Mães treinadas (T e TD) foram submetidas a oito semanas de treinamento físico moderado antes e durante a gestação (60min/dia, cinco dias/sem a 65% do VO2max). Mães desnutridas (D e TD) receberam dieta hipoproteica durante a gestação (8% caseína) enquanto as nutridas (C e T) receberam dieta normoproteica (17% caseína). No primeiro dia pós-natal foi verificado número de filhotes nascidos por ninhada, peso da ninhada e peso ao nascer, eixo látero-lateral do crânio (ELLC) e anteroposterior do crânio (EAPC), eixo longitudinal do corpo (EL) e comprimento da cauda (CC) de cada neonato. No terceito dia pós-parto, os encéfalos foram extraídos e pesados. Durante a gestação, as fêmeas dos grupos T e D apresentaram menor ganho de peso em comparação ao grupo C na terceira semana (C = 34,4 ± 1,3; T = 30,7 ± 0,60; D = 25,8 ± 0,78; TD = 29,9 ± 0,83). Os grupos desnutridos apresentaram menor peso ao nascer em relação aos seus respectivos controles (Cf = 6,3 ± 0,1; Tf = 6,3 ± 0,1; Df = 4,7 ± 0,07; TDf = 5,0 ± 0,06). O grupo Df apresentou as medidas do ELLC (Cf = 9,8 ± 0,06; Tf = 9,8 ± 0,05; Df = 9,2 ± 0,04; TDf = 9,6 ± 0,13) e EAPC (Cf = 18,1 ± 0,1; Tf = 18,2 ± 0,1; Df = 17,5 ± 0,1; TDf = 18,0 ± 0,2) menores comparadas aos filhotes controles. Com base nos resultados, pode-se concluir que a desnutrição no período fetal alterou o desenvolvimento somático enquanto o treinamento físico influenciou positivamente os eixos do crânio dos conceptos

Mechanisms underlying the programming of small artery dysfunction: review of the model using low protein diet in pregnancy in the rat

Human and animal studies have shown that unbalanced maternal nutrition is associated with the development of cardiovascular and metabolic disease in adulthood. In the Southampton maternal low protein model (SMLP), protein deprivation (50%) throughout pregnancy in rats leads to elevated blood pressure in adult offspring. Impaired peripheral arterial function may contribute to the cardiovascular dysfunction observed in these offspring. This review discusses the impact of such a dietary insult on the vascular function of resistance arteries from pregnant rats (pF 0 ), their offspring (F 1 ), the pregnant offspring (pF 1 ) and the second generation (F 2 ). At each stage, disturbances in endothelium-dependent relaxation were observed, implicating changes in endothelial nitric oxide (NO)-guanylate cyclase (GC) signalling pathway in the vascular adaptations to pregnancy and the programmed effects on offspring

The developmental origins of adult disease

Epidemiological and clinical observations have led to the hypothesis that the risk of developing some chronic diseases in adulthood is influenced not only by genetic and adult lifestyle factors, but also by environmental factors acting in early life. These factors act through the processes of developmental plasticity and possibly epigenetic modification, and can be distinguished from developmental disruption. The concept of predictive adaptation has been developed to explain the relationship between early life events and the risk of later disease. At its base, the model suggests that a mismatch between fetal expectation of its postnatal environment and actual postnatal environment contribute to later adult disease risk. This mismatch is exacerbated, in part, by the phenomenon of 'maternal constraint' on fetal growth, which implicitly provides an upper limit of postnatal nutritional environment that humans have adapted for and is now frequently exceeded. These experimental, clinical and conceptual considerations have important implications for prevention and intervention in the current epidemic of childhood obesity and adult metabolic and cardiovascular disorders