Impact of maternal undernutrition and fetal number on glucocorticoid, growth hormone and insulin-like growth factor receptor mRNA abundance in the ovine fetal kidney

Brennan, Kathryn; Gopalakrishnan, G.; Kurlak, Lesia O.; Rhind, S. M.; Kyle, Carol; An, Bo; Rae, Michael T.; Olson, David M.; Stephenson, Terence; Symonds, Michael

doi:10.1530/rep.1.00229

Cited by 42 publications

(36 citation statements)

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“…In the present study, NR between days 66 and 110 gestation enhanced IGF2R mRNA abundance, whereas no effect was seen on IGF1R. Gene expression of IGF1R was raised in the fetal kidney in the absence of any difference in kidney weight or nephron number (Brennan et al 2005). It is, therefore, proposed that these placento-fetal adaptations within the IGF axis could ensure that fetal growth and development are maintained despite a reduction in maternal food intake.…”

Section: Discussionmentioning

confidence: 44%

“…Taken together, these findings indicate that if the level of food intake is kept constant through pregnancy and the mother is able to meet any energy deficit from mobilization of her own body reserves, placenta responses may not be required. However, an increase in fetal fat mass is seen in this group (Brennan et al 2005), that may be indicative of other adaptations within the placento-fetal unit that ultimately contribute to a marked change in adipose tissue function in later life, especially following obesity (Sharkey et al 2009). …”

Section: Discussionmentioning

confidence: 85%

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The differential effects of the timing of maternal nutrient restriction in the ovine placenta on glucocorticoid sensitivity, uncoupling protein 2, peroxisome proliferator-activated receptor-γ and cell proliferation

Yiallourides

Sebért²,

Wilson³

et al. 2009

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Nutrient restriction (NR) during critical windows of pregnancy has differential effects on placento-fetal growth and development. Our study, therefore, investigated developmental and metabolic adaptations within the ovine placenta following NR at different critical windows during the first 110 days of gestation (termZ147 days). Thus, the effects of NR on cell proliferation, glucocorticoid sensitivity, IGF1 and 2 receptor, peroxisome proliferator-activated receptor g (PPARG), and uncoupling protein (UCP)2 gene expression in the placenta were examined. Singleton bearing sheep (nZ4-8 per group) were fed either 100% of their total metabolizable energy requirements throughout the study or 50% of this amount between 0-30, 31-65, 66-110, and 0-110 days gestation. A significant reduction in cell proliferation and increased gene expression for the glucocorticoid and IGF2 receptors, PPARG, and UCP2 were detected in placentae sampled from mothers who were nutrient restricted between days 66 and 110 of gestation, only, relative to controls. This window of gestation coincides with the maximum placental growth and the start of exponential growth of the fetus when there are substantially increased metabolic demands on the placenta compared with earlier in gestation. Consequently, increased glucocorticoid sensitivity and suppressed IGF2 action could contribute to a switch in the placenta from proliferation to differentiation, thereby improving its nutrient transfer capacity. Upregulation of PPARG and UCP2 would promote placental fatty acid metabolism thereby limiting glucose utilization. These compensatory placental responses may serve to maintain fetal growth but could result in adverse adaptations such as the early onset of the metabolic syndrome in later life. Reproduction (2009) 138 601-608

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Section: Discussionmentioning

confidence: 44%

Section: Discussionmentioning

confidence: 85%

The differential effects of the timing of maternal nutrient restriction in the ovine placenta on glucocorticoid sensitivity, uncoupling protein 2, peroxisome proliferator-activated receptor-γ and cell proliferation

Yiallourides

Sebért²,

Wilson³

et al. 2009

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“…This may contribute to the induction of insulin resistance in this model (40) . Altered expression of GR has also been reported in the lung, liver, adrenal and kidney of the offspring of sheep fed a restricted diet during pregnancy (40)(41)(42)(43) . Feeding a PR diet to pregnant rats up-regulates glucokinase expression in the liver of the offspring, which implies increased capacity for glucose uptake (44) .…”

Section: Phenotype Induction and Altered Transcriptionmentioning

confidence: 94%

Effect of maternal diet on the epigenome: implications for human metabolic disease

Lillycrop

2011

Proc. Nutr. Soc.

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The rapid increase in the incidence of chronic non-communicable diseases over the past two decades cannot be explained solely by genetic and adult lifestyle factors. There is now considerable evidence that the fetal and early postnatal environment also strongly influences the risk of developing such diseases in later life. Human studies have shown that low birth weight is associated with an increased risk of CVD, type II diabetes, obesity and hypertension, although recent studies have shown that over-nutrition in early life can also increase susceptibility to future metabolic disease. These findings have been replicated in a variety of animal models, which have shown that both maternal under-and over-nutrition can induce persistent changes in gene expression and metabolism within the offspring. The mechanism by which the maternal nutritional environment induces such changes is beginning to be understood and involves the altered epigenetic regulation of specific genes. The demonstration of a role for altered epigenetic regulation of genes in the developmental induction of chronic diseases raises the possibility that nutritional or pharmaceutical interventions may be used to modify long-term cardio-metabolic disease risk and combat this rapid rise in chronic non-communicable diseases.Epigenetics: DNA methylation: Fetal development: CVD: ObesityThe incidence of chronic non-communicable disease has risen sharply over the last 20 years with an estimated 18 million people dying from CVD per year (1) . This rise in CVD has been amplified by a rapid rise in the rate of obesity and type II diabetes across the world, which are major risk factors for CVD. This increase in the incidence of chronic non-communicable diseases over the past two decades cannot be explained solely by genetic and adult lifestyle factors. There is now substantial evidence that the fetal and early postnatal environment strongly influences the risk of developing cardio-metabolic disease. Epidemiological studies show that a poor intra-uterine environment induced by maternal diet, placental insufficiency or endocrine factors, such as stress, induces changes in the embryo and fetus, which increase its future risk of a range of non-communicable diseases (2) . These findings have been replicated in animal models where restricted nutrition during pregnancy induces dyslipidaemia, obesity, hypertension, hyperinsulinaemia and hyperleptinaemia in the offspring (3,4) . This association between poor intrauterine growth and increased risk of disease in later life may reflect a mismatch between the future environment 'predicted' by the embryo/fetus, based on signals from the mother during gestation, and the actual environment experienced in later life (5) . The mechanism by which cues about nutrient availability in the postnatal environment are transmitted to the fetus and the process by which different, stable phenotypes are induced are beginning to be understood. A number of recent studies suggest that changes in the epigenetic regulation of genes in the embryo ...

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“…NR (nZ5) during the period of maximal placenta growth in sheep i.e. between 30 and 65 days of gestation, as previously described (Brennan et al 2005). At 110 days of gestation, all mothers were euthanized, the fetus weighed, and placentomes randomly sampled for molecular analysis.…”

Section: Animals Diets and Experimental Designmentioning

confidence: 99%

Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression

Sebért¹,

Hyatt²,

Chan³

et al. 2010

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The recent discovery of an association between body composition, energy intake and the fat mass and obesity-associated (FTO) gene represents a promising new therapeutic target in obesity prevention. In a well, pre-established large animal model, we investigated the regulation of FTO gene expression under conditions either leading to obesity or increased risk of obesity related disorders: i) a sedentary 'Western' lifestyle and ii) prenatal exposure to nutrient restriction. Pregnant sheep were either fed to fully meet their nutritional requirements throughout gestation or 50% of this amount from early-to-mid gestation. Following weaning, offspring were either made obese through exposure to a sedentary obesogenic environment or remained lean. A significant positive relationship between placental FTO gene expression and fetal weight was found at 110 days gestation. In both the newborn and adult offspring, the hypothalamus was the major site of FTO gene expression. Hypothalamic FTO gene expression was upregulated by obesity and was further increased by prenatal nutrient restriction. Importantly, we found a strong negative relationship between the hypothalamic FTO gene expression and food intake in lean animals only that may imply FTO as a novel controller of energy intake. In contrast, FTO gene expression in the heart was downregulated in obese offspring born to nutrient restricted mothers. In addition, FTO gene expression was unaffected by obesity or prenatal diet in insulin-dependent tissues, where it changed with age possibly reflecting adaptations in cellular energetic activity. These findings extend information gained from human epidemiology and provide new insights into the regulation of in vivo energy metabolism to prevent obesity.

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Impact of maternal undernutrition and fetal number on glucocorticoid, growth hormone and insulin-like growth factor receptor mRNA abundance in the ovine fetal kidney

Cited by 42 publications

References 25 publications

The differential effects of the timing of maternal nutrient restriction in the ovine placenta on glucocorticoid sensitivity, uncoupling protein 2, peroxisome proliferator-activated receptor-γ and cell proliferation

The differential effects of the timing of maternal nutrient restriction in the ovine placenta on glucocorticoid sensitivity, uncoupling protein 2, peroxisome proliferator-activated receptor-γ and cell proliferation

Effect of maternal diet on the epigenome: implications for human metabolic disease

Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression

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