Intrauterine growth restriction (IUGR) represents an important risk factor for perinatal complications and for adult disease.
IUGR is associated with a down-regulation of placental amino acid ...transporters; however, whether these changes are primary
events directly contributing to IUGR or a secondary consequence is unknown. We investigated the time course of changes in
placental and fetal growth, placental nutrient transport in vivo and the expression of placental nutrient transporters in pregnant rats subjected to protein malnutrition, a model for IUGR.
Pregnant rats were given either a low protein (LP) diet ( n = 64) or an isocaloric control diet ( n = 66) throughout pregnancy. Maternal insulin, leptin and IGF-I levels decreased, whereas maternal amino acid concentrations
increased moderately in response to the LP diet. Fetal and placental weights in the LP group were unaltered compared to control
diet at gestational day (GD) 15, 18 and 19 but significantly reduced at GD 21. Placental system A transport activity was reduced
at GD 19 and 21 in response to a low protein diet. Placental protein expression of SNAT2 was decreased at GD 21. In conclusion,
placental amino acid transport is down-regulated prior to the development of IUGR, suggesting that these placental transport
changes are a cause, rather than a consequence, of IUGR. Reduced maternal levels of insulin, leptin and IGF-1 may link maternal
protein malnutrition to reduced fetal growth by down-regulation of key placental amino acid transporters.
Abstract Maternal obesity and gestational diabetes (GDM) are conditions associated with fetal overgrowth and excessive fat accumulation in the fetus, implicating an increased placental nutrient ...transfer in these pregnancies. Obese and GDM mothers have altered metabolism and hormone levels, including elevation of maternal circulatory lipids and pro-inflammatory cytokines. We tested the hypothesis that interleukin (IL)-6 and tumor necrosis factor (TNF)-α stimulate placental fatty acid transport, as these pro-inflammatory cytokines have been shown to affect lipid metabolism in other tissues. In cultured primary human trophoblast cells IL-6, but not TNF-α, stimulated fatty acid accumulation, as measured by BODIPY fluorescence. The increased fatty acid accumulation could not be explained by an increased expression of key components in placental fatty acid transport, such as adipophilin, fatty acid transport protein (FATP)1, FATP4, or lipoprotein lipase. In a cohort of lean and overweight/obese pregnant women, increasing maternal third trimester IL-6 plasma concentrations correlated with decreasing placental lipoprotein lipase activity. However, as no effect on lipoprotein lipase activity was observed in cultured trophoblast cells after exposure to either IL-6 or TNF-α, the correlation between maternal circulatory IL-6 levels and placental lipoprotein lipase activity at term is unlikely to represent a cause-and-effect relationship. In conclusion, high levels of IL-6 stimulate trophoblast fatty acid accumulation, which could contribute to an excessive nutrient transfer in conditions associated with elevated maternal IL-6 such as obesity and gestational diabetes.
The activity and expression of placental nutrient transporters are primary determinants for the supply of nutrients to the fetus, and these nutrients in turn regulate fetal growth. We developed an ...experimental system to assess amino acid uptake in single primary villous fragments to study hormonal regulation of the amino acid transporter system A in term human placenta. Validation of the method, using electron microscopy and studies of hormone production, indicated that fragments maintained ultrastructural and functional integrity for at least 3 h. The activity of system A was measured as the Na+-dependent uptake of methylaminoisobutyric acid (MeAIB), and the effect of 1 h incubation in various hormones was investigated. Uptake of MeAIB into villous fragments in the presence of Na+ was linear up to at least 30 min. Insulin (300 ng/ml, n = 14) increased system A activity by 56% (P < 0.05). This effect was also present at insulin concentrations in the physiological range (+47% at 0.6 ng/ml, n = 10, P < 0.05). Leptin (500 ng/ml, n = 14) increased Na+-dependent MeAIB uptake by 37% (P < 0.05). System A activity increased in a concentration-dependent fashion in response to leptin (n = 10). However, neither epidermal GF (600 ng/ml), cortisol (340 ng/ml), nor GH (500 ng/ml) altered system A activity significantly (n = 14). We conclude that primary single isolated villous fragments can be used in studies of hormonal regulation of nutrient uptake into the syncytiotrophoblast. These data suggest that leptin regulates system A, a key amino acid transporter.
ABSTRACT
Previous investigations observed a period of major glacial advances in Central Asia during marine oxygen isotope stage (MIS) 3 (57–29 ka), out of phase with global ice volume records. We ...have re‐examined the Kanas moraine complex in the Altai Mountains of Central Asia, where an MIS 3 glaciation had been previously inferred. New and consistent cosmogenic exposure and single‐grain luminescence ages indicate that the Kanas complex was formed during MIS 2 (29–12 ka), which brings its timing in line with the global ice volume record. We also identified a lateral moraine from a more extensive ice extent that dates to late MIS 5/MIS 4. To place our results in a wider contextual framework, we review the chronologies of another 26 proposed major MIS 3 glacial advances in Central Asia. For most of these sites, we find that the chronological data do not provide an unequivocal case for MIS 3 glaciation.
Glacier sediment–landform associations are commonly used as interpretive and predictive tools to reconstruct the nature of past glacial events. Here we provide a regional-scale study of the sediments ...and landforms around the temperate North Patagonian Icefield, an area with outlet glaciers that terminate in the full range of environments possible in a temperate glacier setting (land-terminating, lake-terminating and tidewater-terminating). We present a regional-scale geomorphological map and sedimentological data collected at 11 outlet glaciers of the icefield. Key sediments and landforms include large tracts of ice-scoured bedrock, extensive sandar, terminal moraines, ice-contact glaciofluvial landforms and evidence of paraglacial slope adjustment following glacier recession. The sediments and landforms developed around the North Patagonian Icefield contrast with those previously identified at other temperate outlet glaciers in Iceland and Alaska, and we argue that this is largely a result of topographic controls on glacier terminal environment (e.g. local relief, topography and geomorphological setting).
Aim
The maternal diet during pregnancy and lactation may affect the long‐term health of the offspring. Our aim was to study how a fish or meat diet perinatal and after weaning affects body ...composition, insulin sensitivity and the profile of n‐3 and n‐6 polyunsaturated fatty acids (PUFAs) in breast milk, fat depots, skeletal muscle and liver in male adult mice offspring.
Methods
During gestation and lactation, C57BL/6 dams were fed a herring‐ or beef‐based diet. Half of the pups in each group changed diets after weaning. In offspring, body composition measured by DEXA, plasma lipid profile and insulin sensitivity measured by euglycemic clamp or QUICKI were monitored to adulthood. Analysis of total FAs by GC‐MS were performed in the diet, breast milk and in different tissues.
Results
At 9 week of age, offspring of herring‐fed dams had less body fat than offspring of beef‐fed dams. Mice fed herring after weaning had increased insulin sensitivity at 15 week of age, reduced total plasma cholesterol and triglyceride levels, and compared with beef‐fed mice, larger interscapular brown adipose tissue depots. The FA composition of the maternal diet was mirrored in breast milk, and the herring diet significantly affected the FA profile of different tissues, leading to an increased content of n‐3 PUFAs.
Conclusion
A herring‐based maternal diet reduces body fat in the offspring, but the insulin sensitivity, plasma lipids and amount of brown adipose tissue are affected by the offspring's own diet; the herring diet is more beneficial than the beef diet.
In this paper, we consider the application of Landsat 7 ETM+ imagery and Digital Terrain Models (DTM) for mapping glacial lineaments in a formerly glaciated area of Wales. A series of landform ...interpretation experiments were conducted using different false colour composites (FCC) and a DTM, both individually and in combination. The experiments indicate that the optimal FCC for detection of glacial lineaments at this scale includes the thermal-infrared (TIR) band. However, by performing the interpretation both in the TIR composite and in a visible and near-infrared (VNIR, bands 4, 3, and 2) draped over the DTM, we were able to substantially increase the number of lineaments identified. The glacial lineaments consist of fractured bedrock and are defined as rock drumlins. The landform system formed by these rock drumlins is characterized by convergent flow patterns at its head, attenuated lineaments, and abrupt lateral margins, which may indicate formation by fast-flowing ice.
Thin brittle films on polymer substrates are finding increasing use as gas barriers for example in the medical and food packaging industries and also for the next generation of ultra-light displays ...based on flexible polymer substrates. In order to determine the durability of the barrier under thermal and mechanical loads, test procedures and corresponding data reduction methods are needed to feed the analysis models. One of the tests frequently employed for this kind of multi-layer material systems is the fragmentation test, whose designation comes from the progressively denser pattern of parallel cracks developing when the specimen is loaded under uniaxial tension. From the crack-density versus strain data obtained, a critical strain for crack growth and an assessment of the adhesion of the coating to substrate can be obtained. However, no accepted data reduction methods exist to extract material properties from the test or inversely, successfully predict the crack density as a function of a set of material properties without fitting parameters. In an earlier paper, the authors presented a finite element based analysis methodology to determine the fracture toughness of both the coating and the interface from the fragmentation data. In the simulations, the plastic constitutive behavior of the substrate and the debonding of the coating from the substrate were explicitly included, the latter by use of a cohesive zone model. In this paper an extension of this methodology is presented that enables crack-density evolution with strain to be predicted. The results presented comprise comparisons with experiments to validate the methodology and the influence of (i) coating toughness, (ii) interface toughness and (iii) coating thickness on crack density versus strain.
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