RESUMEN
BACKGROUND: Obesity is associated with lower vitamin D concentrations than normal-weight. Pregnancy may affect vitamin D status, especially in obese subjects. AIMS: The purpose of this study was to compare vitamin D status and intake between obese and normal-weight women during pregnancy. METHODS: Twenty-five obese and 80 normal-weight women were recruited in the Western Sweden region (latitude 57°N). Blood samples and information on diet and sun exposure were collected in each trimester during pregnancy. RESULTS: During summer months, 12% of normal-weight and 50% of obese women in the first trimester had serum 25(OH)D concentrations <50 nmol/L (P < 0.01). Supplement use, body fat mass, season of blood sampling, and travelling to southern latitudes were the most important determinants of vitamin D status. Obese women had higher reported dietary vitamin D intake in early pregnancy compared with normal-weight women. Usage of supplements containing vitamin D was 61% in early pregnancy and declined thereafter. Nine percent of normal-weight and 33% of obese women (P < 0.01) reported a dietary vitamin D intake according to national recommendations in the beginning of pregnancy. CONCLUSIONS: Half of the obese women had what could be considered as suboptimal vitamin D status in early pregnancy and lower vitamin D status compared with normal-weight women despite reporting a higher dietary vitamin D intake. A majority of the women did not reach intake of vitamin D according to dietary recommendations.
Asunto(s)
Obesidad/sangre , Vitamina D/administración & dosificación , Vitamina D/sangre , Composición Corporal , Índice de Masa Corporal , Dieta , Suplementos Dietéticos , Ingestión de Energía , Femenino , Humanos , Fenómenos Fisiologicos Nutricionales Maternos , Embarazo , Estaciones del Año , Luz Solar , SueciaRESUMEN
PURPOSE: Obese subjects have lower circulating 25-hydroxyvitamin D (25(OH)D) than normal-weight subjects. Knowledge is scarce regarding differences in vitamin D-binding protein (DBP), free 25(OH)D, and intake of vitamin D between normal-weight and obese subjects. The purpose of this study was to examine intake and vitamin D status in obese compared with normal-weight women. METHODS: Between September 2009 and October 2011, 43 obese and 43 normal-weight women, 22-45 years of age, mean BMI of 39.1 ± 4.6 and 21.6 ± 1.8 kg/m(2), respectively, were recruited in the western Sweden region (latitude 57°N). Blood samples, data regarding diet, and sun exposure were collected. RESULTS: DBP concentrations were 320 ± 121 and 266 ± 104 µg/mL (P = 0.02) in obese and normal-weight women, respectively. Calculated free 25(OH)D was 13.3 ± 5.5 (obese) and 23.7 ± 10.7 (normal-weight) (P < 0.001). The obese women had a 20.1 nmol/L lower mean 25(HO)D concentration compared to normal-weight women (P < 0.001). 56 % of obese women and 12 % of normal-weight women had 25(OH)D concentrations ≤50 nmol/L. There was no statistically significant difference in total vitamin D intake between the groups. 39 % of the women had a total vitamin D intake <7.5 µg/day, the current national recommendation for vitamin D in Sweden. CONCLUSIONS: Obese women had higher DBP concentrations compared with normal-weight women and lower free 25(OH)D. The obese women were more likely to have 25(OH)D concentrations that could be considered suboptimal. Vitamin D intake was generally low in normal-weight and obese women of childbearing age.
Asunto(s)
Obesidad/sangre , Proteína de Unión a Vitamina D/sangre , Vitamina D/análogos & derivados , Adulto , Composición Corporal , Índice de Masa Corporal , Peso Corporal , Estudios Transversales , Dieta , Suplementos Dietéticos , Ingestión de Energía , Femenino , Humanos , Modelos Lineales , Persona de Mediana Edad , Actividad Motora , Luz Solar , Encuestas y Cuestionarios , Suecia , Vitamina D/administración & dosificación , Vitamina D/sangre , Adulto JovenRESUMEN
CONTEXT: Babies of obese women are often large at birth, which is associated with perinatal complications and metabolic syndrome later in life. The mechanisms linking maternal obesity to fetal overgrowth are largely unknown. OBJECTIVE: We tested the hypothesis that placental insulin/IGF-I and mammalian target of rapamycin (mTOR) signaling is activated and amino acid transporter activity is increased in large babies of obese women. DESIGN AND SETTING: Pregnant women were recruited prospectively for collection of placental tissue at a university hospital and academic biomedical center. PATIENTS OR OTHER PARTICIPANTS: Twenty-three Swedish pregnant women with first trimester body mass index ranging from 18.5 to 44.9 kg/m(2) and with uncomplicated pregnancies participated in the study. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: We determined the phosphorylation of key signaling molecules (including Akt, IRS-1, S6K1, 4EBP-1, RPS6, and AMPK) in the placental insulin/IGF-I, AMPK, and mTOR signaling pathways. The activity and protein expression of the amino acid transporter systems A and L were measured in syncytiotrophoblast microvillous plasma membranes. RESULTS: Birth weights (range, 3025-4235 g) were positively correlated to maternal body mass index (P < 0.05). The activity of placental insulin/IGF-I and mTOR signaling was positively correlated (P < 0.001), whereas AMPK phosphorylation was inversely (P < 0.05) correlated to birth weight. Microvillous plasma membrane system A, but not system L, activity and protein expression of the system A isoform SNAT2 were positively correlated to birth weight (P < 0.001). CONCLUSIONS: Up-regulation of specific placental amino acid transporter isoforms may contribute to fetal overgrowth in maternal obesity. This effect may be mediated by activation of insulin/IGF-I and mTOR signaling pathways, which are positive regulators of placental amino acid transporters.
Asunto(s)
Sistemas de Transporte de Aminoácidos/metabolismo , Macrosomía Fetal/metabolismo , Obesidad/metabolismo , Placenta/metabolismo , Complicaciones del Embarazo/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Adulto , Sistemas de Transporte de Aminoácidos/agonistas , Peso al Nacer/fisiología , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Macrosomía Fetal/etiología , Humanos , Recién Nacido , Factor I del Crecimiento Similar a la Insulina/metabolismo , Obesidad/complicaciones , Obesidad/patología , Placenta/patología , Embarazo , Complicaciones del Embarazo/patología , Transducción de Señal/fisiología , Adulto JovenRESUMEN
Diet is a significant modifiable risk factor for cardiovascular disease and high fish intake has been associated with vascular health in population studies. However, intervention studies have been inconclusive. In this study, male low-density lipoprotein receptor-deficient mice were given 16-week high fat/high sucrose diets, supplemented with either minced herring fillets or minced beef. The diets were matched in total fat and cholesterol content; taurine content and fatty acid composition was analysed. Body weights were recorded throughout the study; plasma lipids were analysed at week 8 and 16. Body composition and adipocyte size were evaluated at study end. Atherosclerosis was evaluated at week 12 (ultrasound) and at termination (en face histology). Herring-fed mice had a higher proportion of long-chain n-3 polyunsaturated fatty acids in the hepatic triacylglycerides (TAG) and phospholipid fractions. The herring-fed mice had increased body weight (P=0.007), and reduced epididymal adipocyte size (P=0.009), despite similar food intake and body composition as the beef-fed mice. The herring-fed mice had lower plasma TAG and very-low-density lipoprotein (VLDL)-cholesterol concentrations throughout the study (TAG; P=0.0012 and 0.004, VLDL-cholesterol; P=0.006 and 0.041, week 8 and 16, respectively). At week 16, the herring-fed had higher plasma concentrations of HDL-cholesterol (P=0.004) and less atherosclerotic lesions in the aortic arch (P=0.007) compared with the beef-fed mice. In conclusion, dietary herring in comparison to beef markedly improved vascular health in this mouse model, suggesting that herring provides an added value beyond its content of macronutrients.
Asunto(s)
Aterosclerosis/dietoterapia , Peces , Lípidos/sangre , Receptores de LDL/genética , Adipocitos/citología , Animales , Aterosclerosis/genética , Aterosclerosis/metabolismo , Peso Corporal , Tamaño de la Célula , Dieta Alta en Grasa , Metabolismo de los Lípidos , Hígado/metabolismo , Masculino , Ratones , Ratones Noqueados , Ratones Obesos , Receptores de LDL/deficienciaRESUMEN
The perinatal environment appears important in establishing metabolic phenotypes in adulthood. Mice deficient in IL-6 (IL-6(-/-)) tend to develop mature-onset obesity, but it is unknown whether perinatal exposure to IL-6 produced by the dam influences the metabolism of adult offspring. To address this issue, we monitored IL-6(-/-) offspring of IL-6(-/-) or IL-6(+/-) dams, as well as wild-type (WT) mice. At adult age, IL-6(-/-) mice weighed significantly more and had more body fat than WT mice, regardless of maternal genotype, and had lower insulin sensitivity. This phenotype was more pronounced in IL-6(-/-) offspring of IL-6(-/-) dams, because they gained weight significantly faster than IL-6(-/-) offspring of IL-6(+/-) dams and had more body fat and higher serum leptin levels at an earlier age. The leptin content was 2-fold higher in milk from IL-6(-/-) than WT dams. However, cross-fostering IL-6(-/-) mice with WT dams did not alter body weight, body composition, or adipocyte size at adult age compared with IL-6(-/-) mice fostered by IL-6(-/-) dams. Conversely, WT mice fostered by IL-6(-/-) dams weighed significantly more than those fostered by WT dams and had more body fat, larger adipocytes, and altered hypothalamic gene expression. We conclude that body fat of adult mice can be increased by perinatal exposure to factors affected by lack of maternal IL-6.
Asunto(s)
Adiposidad/fisiología , Composición Corporal/fisiología , Interleucina-6/deficiencia , Interleucina-6/fisiología , Adipocitos/citología , Adipocitos/metabolismo , Adiposidad/genética , Animales , Composición Corporal/genética , Peso Corporal/genética , Peso Corporal/fisiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnica de Clampeo de la Glucosa , Hipotálamo/metabolismo , Interleucina-6/genética , Leptina/sangre , Masculino , Ratones , Ratones Mutantes , Leche/química , Embarazo , ARN MensajeroRESUMEN
The mechanisms underlying reduced fetal growth in response to maternal protein restriction are not well established. Maternal levels of insulin, IGF-I, and leptin are decreased in rats fed a low protein (LP) diet. Because these hormones stimulate placental amino acid transporters in vitro, we hypothesized that maternal protein restriction inhibits placental leptin, insulin/IGF-I, and mammalian target of rapamycin signaling and down-regulates the expression and activity of placental amino acid transporters. Pregnant rats were fed either an isocaloric low protein (LP, 4% protein) or control diet (18% protein) and studied at gestational day (GD)15, GD19, or GD21 (term 23). At GD19 and GD21, placental expression of phosphorylated eukaryotic initiation factor 4E binding protein 1 (Thr-36/46 or Thr-70) and phosphorylated S6 ribosomal protein (Ser-235/236) was decreased in the LP group. In addition, placental expression of phosphorylated S6 kinase 1 (Thr-389), phosphorylated Akt (Thr-308), and phosphorylated signal transducer and activator of transcription 3 (Tyr-705) was reduced at GD21. In microvillous plasma membranes (MVM) isolated from placentas of LP animals, protein expression of the sodium-coupled neutral amino acid transporter (SNAT)2 and the large neutral amino acid transporters 1 and 2 was reduced at GD19 and GD21. MVM SNAT1 protein expression was reduced at GD21 in LP rats. SNAT4 and 4F2 heavy chain expression in MVM was unaltered. System A and L amino acid transporter activity was decreased in MVM from LP animals at GD19 and GD21. In conclusion, maternal protein restriction inhibits placental insulin, mammalian target of rapamycin signaling, and signal transducer and activator of transcription 3 signaling, which is associated with a down-regulation of placental amino acid transporters. We speculate that maternal endocrine and metabolic control of placental nutrient transport reduces fetal growth in response to protein restriction.
Asunto(s)
Proteínas en la Dieta/farmacología , Regulación de la Expresión Génica/fisiología , Insulina/metabolismo , Placenta/metabolismo , Factor de Transcripción STAT3/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Sistemas de Transporte de Aminoácidos/metabolismo , Animales , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Dieta , Femenino , Peso Fetal , Insulina/genética , Péptidos y Proteínas de Señalización Intracelular , Fenómenos Fisiologicos Nutricionales Maternos , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Fosforilación , Placentación , Embarazo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Proteínas Quinasas S6 Ribosómicas/genética , Proteínas Quinasas S6 Ribosómicas/metabolismo , Factor de Transcripción STAT3/genética , Transducción de Señal , Serina-Treonina Quinasas TOR/genética , Aumento de PesoRESUMEN
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.
Asunto(s)
Adiponectina/sangre , Peso al Nacer , Índice de Masa Corporal , Ingestión de Energía , Hormonas/sangre , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Embarazo/fisiología , Adolescente , Adulto , Dieta , Grasas de la Dieta , Femenino , Peso Fetal , Humanos , Recién Nacido , Entrevistas como Asunto , Placenta/anatomía & histología , Primer Trimestre del Embarazo , Tercer Trimestre del EmbarazoRESUMEN
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.
Asunto(s)
Sistema de Transporte de Aminoácidos L/metabolismo , Retardo del Crecimiento Fetal/metabolismo , Leucina/metabolismo , Placenta/metabolismo , Proteínas Quinasas/metabolismo , Transducción de Señal , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adulto , Sistema de Transporte de Aminoácidos L/efectos de los fármacos , Peso al Nacer , Proteínas de Ciclo Celular , Células Cultivadas , Vellosidades Coriónicas/metabolismo , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Células Epiteliales/metabolismo , Femenino , Retardo del Crecimiento Fetal/patología , Edad Gestacional , Humanos , Inmunohistoquímica , Recién Nacido , Fosfoproteínas/metabolismo , Placenta/efectos de los fármacos , Placenta/patología , Embarazo , Proteínas Quinasas/efectos de los fármacos , Sirolimus/farmacología , Serina-Treonina Quinasas TOR , Trofoblastos/metabolismoRESUMEN
In pregnant women with type 1 diabetes, suboptimal glucose control in the first trimester is a strong predictor for giving birth to a large fetus. However, the mechanisms underlying this association are unknown. We hypothesized that transient hyperglycaemia in early pregnancy results in (1) increased placental growth and (2) an up-regulation of placental nutrient transport capacity, which leads to fetal overgrowth at term. In order to test this hypothesis, pregnant rats were given intraperitoneal injections of glucose (2 g kg(-1), resulting in a 50-100% increase in blood glucose level during 90 min) or saline (control) in either early or late gestation using four different protocols: one single injection on gestational day (GD) 10 (n=5), three injections on GD 10 (n=8-9), six injections on GD 10 and 11 (n=9-11) or three injections on GD 19 (n=7-8). Multiple injections were given approximately 4 h apart. Subsequently, animals were studied on GD 21. Three glucose injections in early pregnancy significantly increased placental weight by 10%, whereas fetal weight was found to be increased at term in response to both three (9% increase in fetal weight, P<0.05) and six glucose injections (7%, P=0.05) in early gestation. A single glucose injection on GD 10 or three injections of glucose on GD 19 had no effect on placental or fetal growth. In groups where a change in feto-placental growth was observed, we measured placental system A and glucose transport activity in the awake animals on GD 21 and placental expression of the glucose and amino acid transporters GLUT1, GLUT3, SNAT2 (system A), LAT1 and LAT 2 (system L). Placental system A transport at term was down-regulated by six glucose injections in early pregnancy (by -33%, P<0.05), whereas placental mRNA and protein levels were unchanged. No long-term alterations in maternal metabolic status were detected. In conclusion, we demonstrate that transient hyperglycaemia in early pregnancy is sufficient to increase fetal weight close to term. In contrast, brief hyperglycaemia in late pregnancy did not stimulate fetal growth. Increased fetal growth may be explained by a larger placenta, which would allow for more nutrients to be transferred to the fetus. These data suggest that maternal metabolic control in early pregnancy is an important determinant for feto-placental growth and placental function throughout the remainder of gestation. We speculate that maternal metabolism in early pregnancy represents a key environmental cue to which the placenta responds in order to match fetal growth rate with the available resources of the mother.
Asunto(s)
Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Diabetes Gestacional/metabolismo , Trastornos Nutricionales en el Feto/etiología , Peso Fetal , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Hiperglucemia/metabolismo , Intercambio Materno-Fetal , Placenta/metabolismo , Sistema de Transporte de Aminoácidos A , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistemas de Transporte de Aminoácidos/metabolismo , Sistemas de Transporte de Aminoácidos Neutros/genética , Animales , Glucemia/metabolismo , Diabetes Gestacional/sangre , Diabetes Gestacional/inducido químicamente , Diabetes Gestacional/patología , Modelos Animales de Enfermedad , Femenino , Trastornos Nutricionales en el Feto/sangre , Trastornos Nutricionales en el Feto/metabolismo , Trastornos Nutricionales en el Feto/patología , Cadenas Ligeras de la Proteína-1 Reguladora de Fusión/metabolismo , Edad Gestacional , Glucosa , Proteínas Facilitadoras del Transporte de la Glucosa/genética , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 3/metabolismo , Hiperglucemia/sangre , Hiperglucemia/inducido químicamente , Hiperglucemia/complicaciones , Hiperglucemia/patología , Insulina/sangre , Transportador de Aminoácidos Neutros Grandes 1/metabolismo , Tamaño de los Órganos , Placenta/patología , Embarazo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
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.
Asunto(s)
Aminoácidos/metabolismo , Dieta con Restricción de Proteínas , Retardo del Crecimiento Fetal/metabolismo , Retardo del Crecimiento Fetal/fisiopatología , Placenta/metabolismo , Sistema de Transporte de Aminoácidos A , Sistemas de Transporte de Aminoácidos/genética , Sistemas de Transporte de Aminoácidos/metabolismo , Aminoácidos/genética , Animales , Transporte Biológico/genética , Transporte Biológico/fisiología , Regulación hacia Abajo/fisiología , Femenino , Regulación de la Expresión Génica/fisiología , Glucosa/metabolismo , Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Leptina/sangre , Placenta/fisiopatología , Embarazo , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/genética , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR , beta-Alanina/análogos & derivados , beta-Alanina/metabolismoRESUMEN
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.