1,721,035 research outputs found

    Placenta, evolution and lifelong health

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    The intrauterine environment has an important influence on lifelong health, and babies who grew poorly in the womb are more likely to develop chronic diseases in later life. Placental function is a major determinant of fetal growth and is therefore also a key influence on lifelong health. The capacity of the placenta to transport nutrients to the fetus and regulate fetal growth is determined by both maternal and fetal signals. The way in which the placenta responds to these signals will have been subject to evolutionary selective pressures. The responses selected are those which increase Darwinian fitness, i.e. reproductive success. This review asks whether in addition to responding to short-term signals, such as a rise in maternal nutrient levels, the placenta also responds to longer-term signals representing the mother’s phenotype as a measure of environmental influences across her life course. Understanding how the placenta responds to maternal signals is therefore not only important for promoting optimal fetal growth but can also give insights into how human evolution affected developmental history with long-term effects on health and disease

    The mechanisms and regulation of placental amino acid transport to the human foetus

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    The mechanisms by which amino acids are transferred across the human placenta are fundamental to our understanding of foetal nutrition. Amino acid transfer across the human placenta is dependent on transport across both the microvillous and basal plasma membranes of the placental syncytiotrophoblast, and on metabolism within the syncytiotrophoblast. Although the principles underlying uptake of amino acids across the microvillous plasma membrane are well understood, the extent to which amino acids are metabolised within human placenta and the mechanisms by which amino acids are transported out of the placenta across the basal plasma membrane are not well understood. Understanding the mechanisms and regulation of amino acid transport is necessary to understand the causes of intrauterine growth restriction in human pregnancy

    Effects of maternal iron restriction in the rat on hypoxia-induced gene expression and fetal metabolite levels

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    The mechanism by which maternal Fe deficiency in the rat causes fetal growth retardation has not been clearly established. This study compared the effects on the fetuses from dams fed a control diet with two groups of dams fed Fe-restricted diets. One Fe-restricted group was fed the Fe-restricted diet for 1 week prior to mating and throughout gestation and the second Fe-restricted group was fed the Fe-restricted diet for 2 weeks prior to mating and throughout gestation. On day 21 of gestation Fe-restricted dams, and their fetuses, were anaemic. Fetal weight was reduced in both Fe-restricted groups compared with controls. Expression of hypoxia-inducible factor (HIF)-1 and vascular endothelial growth factor (VEGF) are induced by hypoxia. The levels of HIF-1 mRNA were highest in placenta, then in kidney, heart and liver but were not different between the groups. Levels of plasma VEGF were not different between the groups. Maternal plasma triacylglycerol was decreased in the 1-week Fe-restricted dams compared with controls. Maternal plasma cholesterol and free fatty acid levels were not different between the groups. In fetal plasma, levels of triacylglycerol and cholesterol were decreased in both Fe-restricted groups. In maternal plasma, levels of a number of amino acids were elevated in both Fe-restricted groups. In contrast, levels of a number of amino acids in fetal plasma were lower in both Fe-restricted groups. Fetal plasma lactate was increased in Fe-restricted fetuses but fetal plasma glucose and -hydroxybutyrate were not affected. These changes in fetal metabolism may contribute to fetal growth retardation in this model. This study does not support the hypothesis that the Fe-restricted fetus is hypoxic

    Effects of maternal iron restriction in the rat on blood pressure, glucose tolerance, and serum lipids in the 3-month-old offspring

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    Epidemiologic studies have demonstrated associations between low birth weight and increased rates of adult diseases such as hypertension and diabetes. Maternal iron restriction in the rat has been reported to both reduce birth weight and to elevate blood pressure at 40 days of age. The aim of the present study was to extend these findings to investigate the effects of maternal iron restriction on glucose tolerance and serum lipids, 2 important components of the metabolic syndrome, in adult offspring. Blood pressure, glucose tolerance, and serum lipids were measured in the 3-month-old offspring of iron-restricted dams. Rats were placed on control or iron-restricted diets 1 week before mating. At term, dams on the iron-restricted diet were anemic with decreased haemoglobin, red blood cell (RBC) count, hematocrit, and mean RBC volume compared with controls. Neonates from iron-restricted litters were more severely anemic than the dams. At birth, body weight was lower in the offspring of iron-restricted dams than in controls and was still decreased at 3 months of age. At this same age, systolic blood pressure was significantly elevated in the offspring of iron-restricted dams. Glucose tolerance was improved in the maternal iron-restricted group. Fasting serum insulin levels were not different between the control and maternal iron-restricted groups. Fasting serum triglyceride was decreased in the offspring of iron-restricted dams compared with controls. Fasting serum cholesterol and free fatty acid concentrations were similar in both groups. These results suggest that maternal iron restriction has long-term effects on physiology and metabolism in the offspring. Some of these findings are comparable to those reported for the maternal protein-restriction model. It is thus speculated that the long-term effects of maternal dietary restriction may result from common fetal metabolic responses to this restriction

    Sex differences in the mRNA levels of housekeeping genes in human placenta

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    In our recent letter to Placenta we reported the expression stability of mRNA for 12 potential housekeeping genes in placental tissue using the geNorm system [1] J.K. Cleal, P. Day, M.A. Hanson and R.M. Lewis, Measurement of housekeeping genes in human placenta, Placenta (2009).[1]. We identified three which had the most stable mRNA expression and recommended these for use in studies on human placenta.We have subsequently analysed the mRNA levels of these housekeeping genes by quantitative real-time rtPCR in 102 human placentas from the Southampton Women’s Survey [2]. With the larger sample size it became apparent that all three housekeeping genes were expressed at a higher level in male placentas (n = 53) than in female placentas (n = 49): UBC 19.8 (18.6–20.9) vs 17.8 (16.3–19.3), p = 0.035; TOP1 22.8 (21.7–23.8) vs 19.7 (18.4–20.9), p = 0.0002; YWHAZ 19.25 (18.4–20.1) vs 17.6 (16.7–18.6), p = 0.014, data is mean and 95% CI (arbitrary units) in male and female placentas respectively. This interesting observation has implications for our understanding of placental biology as well as questioning the suitability of these genes for use as housekeeping genes where male and female placentas are being analysed together.<br/

    Long-term programming of blood pressure by maternal dietary iron restriction in the rat

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    We have reported that blood pressure was elevated in 3-month-old rats whose mothers were Fe-restricted during pregnancy. These animals also had improved glucose tolerance and decreased serum triacylglycerol. The aim of the present study was to determine whether these effects of maternal nutritional restriction, present in these animals at 3 months of age, can be observed in the same animals in later life. Pulmonary and serum angiotensin converting enzyme (ACE) concentrations were also measured to investigate whether the renin-angiotensin system was involved in the elevation of blood pressure observed in the offspring of Fe-restricted dams. Systolic blood pressure was higher in the offspring of Fe-restricted dams at 16 months of age. Heart and kidney weight were increased as a proportion of body weight in the offspring of Fe-restricted dams. The pulmonary ACE concentration was not significantly different between the groups. The serum ACE concentration was significantly elevated in the offspring of Fe-restricted dams at 3 but not 14 months of age. There was a strong correlation between serum ACE levels at 3 and 14 months of age. Glucose tolerance and serum insulin were not different between the maternal diet groups. Serum triacylglycerol tended to be lower in the offspring of Fe-restricted dams. There were no differences in serum non-esterified fatty acids or serum cholesterol between the maternal diet groups. This study provides further evidence that maternal nutrition has effects on the offspring that persist throughout life. At 16 months of age, the elevation of blood pressure in Fe-restricted offspring does not appear to be mediated via changes in ACE levels. Both cardiac hypertrophy and decreased serum triacylglycerol have also been observed in Fe-restricted fetuses, suggesting that these changes may be initiated in utero

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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