Related to heart size [100]. (3) The numbers of secondary muscle fibres has been reported in the young offspring of a variety of species, including rats [101], pigs [102] and sheep [103] following maternal undernutrition during the critical proliferative period for muscle fibre development.Nutrients 2015,(4) Total pancreatic weight, islet cell mass and the relative proportion of -cells within the islets [104] has been reported to be lower in IUGR rat offspring. Furthermore, it has been shown that the vasculature undergoes permanent changes in reactivity as a result of maternal nutrient restriction [105]. In addition, there are reports of persistent alterations of the hypothalamic-pituitary-adrenal (HPA) axis of IUGR rat offspring [106,107] and this is postulated to play a critical role in the observed association between foetal growth restriction and subsequent cardiovascular and metabolic diseases. Figure 1 collectively shows the sequence of events that can potentially lead to the programming for increased risk of cardiovascular disease in IUGR offspring. 6. Animal Model of IUGR–Maternal Quinagolide (hydrochloride) solubility protein Restriction in Rats Much of our knowledge relating to the short term and long-term effects of IUGR has been derived from animal studies. A number of animal models of poor maternal nutrition and/or placental insufficiency have been developed over recent years to investigate the causes and consequences of IUGR. A variety of species have been studied, including: rodents, sheep and primates; and both, maternal dietary manipulations or surgical interventional techniques have been employed [108?14]. One of the most extensively studied and well-characterised animal models is maternal protein restriction in rats. Regardless of how severe the protein restriction is (mild- 9 diet or severe- 5 diet) the end result is reduction in body NVP-AUY922 price weight of the offspring [115?19]. In our laboratory over the past decade we have comprehensively examined the cardiovascular phenotype of rat offspring following maternal protein restriction. However, as our studies have progressed, it has become clearly apparent, that the cardiovascular and metabolic phenotype of the offspring using this model differs between different laboratories, which likely relates to subtle differences in study design. This in turn, makes comparison of the findings between studies difficult. For example, there are differences in the strain of rats studied, levels of maternal protein restriction in the diet, timing of administration of the diet to the dams and postnatal differences in body growth and levels of blood pressure of the offspring. These differences are highlighted in Table 1. In our studies, Wistar-Kyoto (WKY) female breeder rats are fed a low protein diet for two weeks prior to birth to get the dams accustomed to the diet, then during pregnancy and for two weeks during lactation as the rodent organ systems are still developing in the early postnatal period. To avoid a high mortality rate in the offspring [120] we have chosen moderate protein restriction (8.7 casein in the diet) for the dams [121?28], rather than a more severe protein deprivation (6 casein) that is sometimes used by other investigators [129?31]. In the following sections we compare our findings with others; in doing so, we highlight differences in the maternal protein restriction model, which may account for conflicting findings between laboratories (Table 1).Nutrients 2015, 7 Table 1. Studies investigating the effects.Related to heart size [100]. (3) The numbers of secondary muscle fibres has been reported in the young offspring of a variety of species, including rats [101], pigs [102] and sheep [103] following maternal undernutrition during the critical proliferative period for muscle fibre development.Nutrients 2015,(4) Total pancreatic weight, islet cell mass and the relative proportion of -cells within the islets [104] has been reported to be lower in IUGR rat offspring. Furthermore, it has been shown that the vasculature undergoes permanent changes in reactivity as a result of maternal nutrient restriction [105]. In addition, there are reports of persistent alterations of the hypothalamic-pituitary-adrenal (HPA) axis of IUGR rat offspring [106,107] and this is postulated to play a critical role in the observed association between foetal growth restriction and subsequent cardiovascular and metabolic diseases. Figure 1 collectively shows the sequence of events that can potentially lead to the programming for increased risk of cardiovascular disease in IUGR offspring. 6. Animal Model of IUGR–Maternal Protein Restriction in Rats Much of our knowledge relating to the short term and long-term effects of IUGR has been derived from animal studies. A number of animal models of poor maternal nutrition and/or placental insufficiency have been developed over recent years to investigate the causes and consequences of IUGR. A variety of species have been studied, including: rodents, sheep and primates; and both, maternal dietary manipulations or surgical interventional techniques have been employed [108?14]. One of the most extensively studied and well-characterised animal models is maternal protein restriction in rats. Regardless of how severe the protein restriction is (mild- 9 diet or severe- 5 diet) the end result is reduction in body weight of the offspring [115?19]. In our laboratory over the past decade we have comprehensively examined the cardiovascular phenotype of rat offspring following maternal protein restriction. However, as our studies have progressed, it has become clearly apparent, that the cardiovascular and metabolic phenotype of the offspring using this model differs between different laboratories, which likely relates to subtle differences in study design. This in turn, makes comparison of the findings between studies difficult. For example, there are differences in the strain of rats studied, levels of maternal protein restriction in the diet, timing of administration of the diet to the dams and postnatal differences in body growth and levels of blood pressure of the offspring. These differences are highlighted in Table 1. In our studies, Wistar-Kyoto (WKY) female breeder rats are fed a low protein diet for two weeks prior to birth to get the dams accustomed to the diet, then during pregnancy and for two weeks during lactation as the rodent organ systems are still developing in the early postnatal period. To avoid a high mortality rate in the offspring [120] we have chosen moderate protein restriction (8.7 casein in the diet) for the dams [121?28], rather than a more severe protein deprivation (6 casein) that is sometimes used by other investigators [129?31]. In the following sections we compare our findings with others; in doing so, we highlight differences in the maternal protein restriction model, which may account for conflicting findings between laboratories (Table 1).Nutrients 2015, 7 Table 1. Studies investigating the effects.