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- Ericsson, Anette, 1975, et al.
(författare)
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Hormonal regulation of glucose and system A amino acid transport in first trimester placental villous fragments.
- 2005
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Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 288:3
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Tidskriftsartikel (refereegranskat)abstract
- Alterations in placental nutrient transfer have been implicated in fetal growth abnormalities. In pregnancies complicated by diabetes and accelerated fetal growth, upregulations of glucose transporter 1 (GLUT1) and amino acid transporter system A have been shown in the syncytiotrophoblast of term placenta. In contrast, intrauterine growth restriction is associated with a downregulation of placental system A transporters. However, underlying mechanisms of transporter regulation are poorly understood, particularly in early pregnancy. In this study, hormonal regulation of placental glucose and system A transporters was investigated. The uptake of 3-O-[methyl-(14)C]-d-glucose was studied in villous fragments isolated from first trimester (6-13 wk of gestation) and term human placenta. Villous fragments were incubated in buffer containing insulin, leptin, cortisol, growth hormone (GH), prolactin, IGF-I, or under hypo/hyperglycemic conditions for 1 h. Subsequently, 3-O-[methyl-(14)C]-D-glucose uptake was measured with and without phloretin for 70 s in first trimester tissue and 20 s in term tissue. Methylaminoisobutyric uptake was measured with and without Na+ for 20 min. Glucose uptake was unaltered by hormones or hypo/hyperglycemia. GH decreased system A activity by 31% in first trimester (P < 0.05). The uptake of glucose was 50% higher in term compared with first trimester fragments and increased markedly between 6 and 13 wk of gestation (P < 0.05). We conclude that placental glucose transporter activity is not regulated by short exposures to the hormones or glucose concentrations tested. In contrast to term placental villous fragments, system A activity was not regulated by insulin or leptin in first trimester but was downregulated by GH.
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- Jansson, Nina, 1976, et al.
(författare)
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Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet.
- 2006
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Ingår i: The Journal of physiology. - : Wiley. - 0022-3751. ; 576:Pt 3, s. 935-46
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Jansson, Nina, 1976, et al.
(författare)
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Maternal hormones linking maternal body mass index and dietary intake to birth weight.
- 2008
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Ingår i: American Journal of Clinical Nutrition. - Bethesda, USA : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 87:6, s. 1743-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obese women often give birth to large-for-gestational age infants (typically defined as a birth weight greater than the 90th percentile), who are at risk of birth injuries and of developing metabolic syndrome later in life. The mechanisms underlying increased fetal growth remain to be established. OBJECTIVE: We aimed to identify maternal hormones that can explain the link between dietary intake, body mass index (BMI), and birth weight. DESIGN: Pregnant women with BMIs (in kg/m(2)) ranging from 17 to 44 (n = 49) were recruited in gestational weeks 8-12. Serum hormone concentrations were measured and dietary history interviews were performed in the first and third trimesters. Multiple regression models were produced to identify hormones that correlate with birth weight and are influenced by BMI or dietary factors. RESULTS: We found a strong positive correlation between BMI and first- and third-trimester insulin and leptin concentrations and a negative correlation between BMI and first-trimester adiponectin and first- and third-trimester insulin-like growth factor binding protein-1 (IGFBP-1). Maternal total fat intake in the first trimester was positively correlated with maternal leptin and inversely correlated with adiponectin. In addition, third-trimester total fat intake was positively correlated with circulating resistin concentrations. First-trimester maternal serum resistin was positively correlated with birth weight, whereas third-trimester maternal IGFBP-1 was negatively correlated with birth weight. CONCLUSIONS: High first-trimester maternal serum resistin and low third-trimester IGFBP-1 were correlated with increased birth weight. We propose that low serum concentrations of IGFBP-1 represent a link between high BMI and increased fetal growth by increasing the bioavailability of insulin-like growth factor-I, which up-regulates placental nutrient transport.
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- Roos, Sara, 1979, et al.
(författare)
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Mammalian target of rapamycin in the human placenta regulates leucine transport and is down-regulated in restricted fetal growth.
- 2007
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Ingår i: The Journal of physiology. - : Wiley. - 0022-3751. ; 582:Pt 1, s. 449-59
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Tidskriftsartikel (refereegranskat)abstract
- Pathological fetal growth is associated with perinatal morbidity and the development of diabetes and cardiovascular disease later in life. Placental nutrient transport is a primary determinant of fetal growth. In human intrauterine growth restriction (IUGR) the activity of key placental amino acid transporters, such as systems A and L, is decreased. However the mechanisms regulating placental nutrient transporters are poorly understood. We tested the hypothesis that the mammalian target of rapamycin (mTOR) signalling pathway regulates amino acid transport in the human placenta and that the activity of the placental mTOR pathway is reduced in IUGR. Using immunohistochemistry and culture of trophoblast cells, we show for the first time that the mTOR protein is expressed in the transporting epithelium of the human placenta. We further demonstrate that placental mTOR regulates activity of the l-amino acid transporter, but not system A or taurine transporters, by determining the mediated uptake of isotope-labelled leucine, methylaminoisobutyric acid and taurine in primary villous fragments after inhibition of mTOR using rapamycin. The protein expression of placental phospho-S6K1 (Thr-389), a measure of the activity of the mTOR signalling pathway, was markedly reduced in placentas obtained from pregnancies complicated by IUGR. These data identify mTOR as an important regulator of placental amino acid transport, and provide a mechanism for the changes in placental leucine transport in IUGR previously demonstrated in humans. We propose that mTOR functions as a placental nutrient sensor, matching fetal growth with maternal nutrient availability by regulating placental nutrient transport.
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