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1
Chandler, K. D., B. J. Leury, A. R. Bird, and A. W. Bell. "Effects of undernutrition and exercise during late pregnancy on uterine, fetal and uteroplacental metabolism in the ewe." British Journal of Nutrition 53, no. 3 (May 1985): 625–35. http://dx.doi.org/10.1079/bjn19850072.
Анотація:
1. Uterine, umbilical and, by difference, uteroplacental net uptakes of oxygen, glucose, lactate and 3-hydroxybutyrate (uterine uptake only) were measured in single-pregnant ewes which were either well-fed throughout, or severely undernourished for 8–20 d during late pregnancy. All animals were studied while standing at rest and then while walking on a treadmill at 0.7 m/s on a 10° slope for 60 min.2. Undernutrition did not significantly affect fetal or placental weights at 143 d gestation but caused a 14% decrease in maternal live weight. Uterine blood flow was decreased by 32% and was associated with a significant decrease in uteroplacental oxygen uptake; neither umbilical blood flow nor fetal O2, uptake were affected by maternal plane of nutrition. Maternal and fetal hypoglycaemia in underfed ewes was accompanied by 46–63 % decreases in uterine, umbilical and uteroplacental net uptakes of glucose, and similar declines in uterine and umbilical glucose/O, quotients. Moderate maternal hyperketonaemia was associated with 2.5-fold and 3-fold increases in uterine net uptake of 3-hydroxybutyrate and 3-hydroxybutyrate/O2 quotient respectively.3. Exercise caused significant decreases in uterine blood flow in fed and underfed ewes but did not affect uterine or umbilical O2 uptakes; uterine net glucose uptake increased in most ewes but umbilical uptake was not significantly affected. Umbilical net uptake of lactate was significantly reduced. In underfed ewes, the extent of hyperketonaemia was significantly reduced by exercise.4. Contrary to earlier proposals, the ovine pregnant uterus is sensitive and adaptable to long- and short-term alterations in maternal energy balance, as achieved by chronic undernutrition and exercise respectively. Thus, the fetus and placenta significantly add to, but do not necessarily have priority over the energy demands of other tissues of the ewe.
2
Leury, B. J., A. R. Bird, K. D. Chandler, and A. W. Bell. "Glucose partitioning in the pregnant ewe: Effects of undernutrition and exercise." British Journal of Nutrition 64, no. 2 (September 1990): 449–62. http://dx.doi.org/10.1079/bjn19900045.
Анотація:
Maternal whole-body glucose entry rate and uterine and umbilical net uptakes of glucose and oxygen were measured in single-pregnant ewes which were either well-fed throughout, or fed at 0.3–0.4 predicted energy requirement for 7–21 d during late pregnancy. All ewes were studied while standing at rest and then while walking on a treadmill at 0.7 m/s on a 10° slope for 60 min. Underfed ewes suffered significant decreases in live weight and had lower fetal, but not placental, weights at 140–144 d gestation. Undernutrition also caused large decreases in maternal glycaemia and glucose entry rate, which were associated with equally large decreases in uterine and umbilical net uptakes and O2 quotients of glucose, and with a decrease in placental glucose transfer capacity. Exercise caused increases in maternal blood concentration, entry rate and uterine net uptake of glucose, the magnitudes of which were not significantly affected by plane of nutrition. Umbilical glucose uptake and placental glucose transfer capacity increased during exercise in underfed but not fed ewes. The fractional distribution of maternal glucose to the pregnant uterus, and of uterine glucose uptake to the fetus, were unaltered by undernutrition; during exercise, a disproportionately small fraction of the increased maternal glucose supply went to the uterus. The results confirm that the ovine conceptus responds to nutritional reduction in maternal glucose availability in a manner similar to non-uterine maternal tissues. Major reductions in glucose supply appear to override putative glucose-sparing mechanisms which may operate to favour the conceptus in better-nourished animals.
3
Bell, A. W., J. M. Kennaugh, F. C. Battaglia, E. L. Makowski, and G. Meschia. "Metabolic and circulatory studies of fetal lamb at midgestation." American Journal of Physiology-Endocrinology and Metabolism 250, no. 5 (May 1, 1986): E538—E544. http://dx.doi.org/10.1152/ajpendo.1986.250.5.e538.
Анотація:
Uterine and umbilical blood flows, the placental clearance of 3H2O, uterine and umbilical uptakes of oxygen, glucose, and lactate were measured in conscious, pregnant sheep at 71-81 days gestation. Fetal weight was 210 +/- 20 g and less than half placental weight. In relation to fetal weight, umbilical flow was 468 +/- 57 ml X min-1 X kg-1, more than double normal values for the mature fetus. Clearance of 3H2O was approximately 12% of the late pregnancy value but high in relation to fetal weight (280 +/- 23 ml X min-1 X kg-1). Fetal oxygen uptake was 10.9 +/- 0.6 ml X min-1 X kg-1, approximately 40% greater than in late gestation. Umbilical uptake of glucose was also relatively high, whereas lactate uptake was low. Uteroplacental tissues consumed more than 80% of the oxygen and glucose taken up by the pregnant uterus. However, uteroplacental utilization rates of oxygen and glucose as well as net lactate production were lower (approximately 50, 30, and 25%, respectively) than in late pregnancy, despite a larger placental mass (486 +/- 22 vs. 302 +/- 12 g).
4
Das, Utpala G., Jing He, Richard A. Ehrhardt, William W. Hay, and Sherin U. Devaskar. "Time-dependent physiological regulation of ovine placental GLUT-3 glucose transporter protein." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 279, no. 6 (December 1, 2000): R2252—R2261. http://dx.doi.org/10.1152/ajpregu.2000.279.6.r2252.
Анотація:
We immunolocalized the GLUT-3 glucose transporter isoform versus GLUT-1 in the late-gestation epitheliochorial ovine placenta, and we examined the effect of chronic maternal hyperglycemia and hypoglycemia on placental GLUT-3 concentrations. GLUT-3 was limited to the apical surface of the trophoectoderm, whereas GLUT-1 was on the basolateral and apical surfaces of this cell layer and in the epithelial cells lining the placental uterine glands. GLUT-3 concentrations declined at 17–20 days of chronic hyperglycemia ( P < 0.05), associated with increased uterine and uteroplacental net glucose uptake rate, but a normal fetal glucose uptake rate was observed. Chronic hypoglycemia did not change GLUT-3 concentrations, although uterine, uteroplacental, and fetal net glucose uptake rates were decreased. Thus maternal hyperglycemia causes a time-dependent decline in the entire placental glucose transporter pool (GLUT-1 and GLUT-3). In contrast, maternal hypoglycemia decreases GLUT-1 but not GLUT-3, resulting in a relatively increased GLUT-3 contribution to the placental glucose transporter pool, which could maintain glucose delivery to the placenta relative to the fetus when maternal glucose is low.
5
Hooper, S. B., D. W. Walker, and R. Harding. "Oxygen, glucose, and lactate uptake by fetus and placenta during prolonged hypoxemia." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 268, no. 2 (February 1, 1995): R303—R309. http://dx.doi.org/10.1152/ajpregu.1995.268.2.r303.
Анотація:
Our aim was to compare the effects of short (4 h) and prolonged (24 h) periods of reduced uterine blood flow (RUBF) on fetal and placental uptake of O2, glucose, and lactate. In pregnant sheep, uterine and umbilical blood flows were measured under normal conditions and after 4 and 24 h of RUBF. A 50% reduction in uterine blood flow caused a 56% reduction in fetal arterial O2 saturation (SaO2). Umbilical blood flow increased from 325 +/- 33 to 378 +/- 32 ml.min-1.kg-1 (P < 0.05) after 4 h but was not different from pre-RUBF values after 24 h. O2 uptake by the gravid uterus was not altered by RUBF, due to an increase (84%) in uterine O2 extraction. Similarly, uteroplacental and fetal O2 consumptions and fetal glucose uptake were not affected by RUBF, whereas uteroplacental glucose uptake was significantly reduced after 4 h (by 42%) and 24 h (by 58%) of RUBF. Fetal lactate uptake was greatly reduced from 78.7 +/- 15.5 to -167 +/- 57 mumol.min-1.kg-1 after 4 h and to -198 +/- 80 mumol.min-1.kg-1 after 24 h of RUBF; negative values indicate placental lactate uptake from the fetal circulation. Thus, although RUBF significantly reduced fetal SaO2, fetal and uteroplacental O2 consumptions did not change. In addition, although fetal glucose uptake was not altered by RUBF, during RUBF the placenta became a major site of lactate clearance from the fetal circulation.
6
Reynolds, L. P., C. L. Ferrell, Debra A. Robertson, and S. P. Ford. "Metabolism of the gravid uterus, foetus and utero-placenta at several stages of gestation in cows." Journal of Agricultural Science 106, no. 3 (June 1986): 437–44. http://dx.doi.org/10.1017/s0021859600063309.
Анотація:
SummaryTo quantify changes in rates of metabolism and nutrient uptake of gravid uteiine, foetal and utero-placental tissues throughout gestation, mature Hereford cows received surgery at 132 ± 0·6 (n = 12), 176 ± 0·5 (n = 8), 220 ±0·4 (n = 11) and 245 ±1·5 (n = 7) days after mating. Indwelling catheters were implanted into a uterine artery and vein of all cows. Foetal catheters also were implanted into an umbilical vein and foetal femoral artery and vein (days 176 and 220) or into a placental artery and two placental veins (days 132 and 245). Approximately 5 days after surgery, deuterium oxide was infused into a foetal femoral venous or placental venous catheter during a 3 h period to quantify uterine and umbilical blood flows by steady-state diffusion methods. Oxygen, glucose, lactate and α-amino acid nitrogen concentrations were determined for uterine and foetal blood samples collected during this procedure.Uterine blood flow increased 4·5-fold (2·92–13·181/min) and umbilical blood flow increased 21-fold (0·28–5·861–min) during the interval of gestation studied. The relative rate of increase of umbilical blood flow was about twice as great as that of uterine blood flow. Uterine arterial and umbilical venous concentrations as well as uterine arterial-venous and umbilical venous-arterial concentration differences in metabolites changed little with stage of gestation. However, because rates of blood flow increased, uptakes of O2, glucose and α-amino N by the gravid uterus and foetus increased as gestation advanced. The proportion of gravid uterine uptakes utilized by the foetus increased from day 137 to 226 for O2 (24–58%) and from day 137 to 180 for glucose (4–19%), then remained relatively constant. The proportion of gravid uterine α-amino N uptake utilized by the foetus remained relatively constant and averaged 60%. A net secretion of lactate from the utero-placenta to the uterine and foetal circulations was observed and increased as gestation advanced. These data indicate that increased rates of uptake or secretion of metabolites by tissues of the gravid uterus can be explained primarily by increased rates of uterine and umbilical blood flows.
7
Trotta, Ronald J., Manuel A. Vasquez-Hidalgo, Brandon I. Smith, Sarah A. Reed, Kristen E. Govoni, Kimberly A. Vonnahme, and Kendall C. Swanson. "248 Maternal Nutrient Restriction During Mid-gestation Decreases Uteroplacental Release and Fetal Uptake of Essential Amino Acids in Sheep." Journal of Animal Science 99, Supplement_3 (October 8, 2021): 130–31. http://dx.doi.org/10.1093/jas/skab235.238.
Анотація:
Abstract To examine the effects of maternal nutrient restriction on net uteroplacental flux during mid-gestation, 14 singleton ewes (48.2 ± 4.0 kg body weight) were fed 100% (control; CON; n = 7) or 60% of nutrient requirements (restricted; RES; n = 7) from day 50–90 (mid-gestation). On day 90, uteroplacental blood flow was measured via Doppler ultrasonography and blood samples were collected from the femoral artery, uterine vein, umbilical artery, and umbilical vein. Blood vessel glucose and amino acids (AA) concentrations were measured and arterial-venous (uterine, AV; fetal, va) differences and net fluxes were calculated. Data were analyzed using the GLM procedure of SAS for effects of treatment. Nutrient restriction during mid-gestation did not influence (P ≥ 0.17) uterine or umbilical blood flows. Uterine AV and fetal va differences of total, essential, and nonessential AA were not influenced (P > 0.10) by nutrient restriction. Nutrient restriction decreased (P ≤ 0.05) uterine and uteroplacental release of total AA and tended to decrease (P = 0.07) total AA uptake by the fetus. Uteroplacental release and fetal uptake of essential AA were decreased (P = 0.03) with RES by 53.4% and 45%, respectively. Uterine and uteroplacental release of nonessential AA were decreased (P = 0.03) with RES but, fetal uptake was not affected (P = 0.14). Nutrient restriction decreased (P ≤ 0.04) fetal uptake of methionine, phenylalanine, threonine, and valine and tended to decrease (P ≤ 0.10) fetal uptake of isoleucine, leucine, and tryptophan. Umbilical artery glucose concentrations were 32% lesser (P = 0.01) with RES and RES tended to increase (P = 0.08) fetal glucose uptake. Nutrient restriction during mid-gestation altered uteroplacental and fetal flux of AA in the current study. The results may indicate that fetal metabolism shifts to adapt to reduced AA supply which results in greater glucose utilization.
8
Tanner, Amelia R., Cameron S. Lynch, Victoria C. Kennedy, Asghar Ali, Quinton A. Winger, Paul J. Rozance, and Russell V. Anthony. "CSH RNA Interference Reduces Global Nutrient Uptake and Umbilical Blood Flow Resulting in Intrauterine Growth Restriction." International Journal of Molecular Sciences 22, no. 15 (July 29, 2021): 8150. http://dx.doi.org/10.3390/ijms22158150.
Анотація:
Deficiency of the placental hormone chorionic somatomammotropin (CSH) can lead to the development of intrauterine growth restriction (IUGR). To gain insight into the physiological consequences of CSH RNA interference (RNAi), the trophectoderm of hatched blastocysts (nine days of gestational age; dGA) was infected with a lentivirus expressing either a scrambled control or CSH-specific shRNA, prior to transfer into synchronized recipient sheep. At 90 dGA, umbilical hemodynamics and fetal measurements were assessed by Doppler ultrasonography. At 120 dGA, pregnancies were fitted with vascular catheters to undergo steady-state metabolic studies with the 3H2O transplacental diffusion technique at 130 dGA. Nutrient uptake rates were determined and tissues were subsequently harvested at necropsy. CSH RNAi reduced (p ≤ 0.05) both fetal and uterine weights as well as umbilical blood flow (mL/min). This ultimately resulted in reduced (p ≤ 0.01) umbilical IGF1 concentrations, as well as reduced umbilical nutrient uptakes (p ≤ 0.05) in CSH RNAi pregnancies. CSH RNAi also reduced (p ≤ 0.05) uterine nutrient uptakes as well as uteroplacental glucose utilization. These data suggest that CSH is necessary to facilitate adequate blood flow for the uptake of oxygen, oxidative substrates, and hormones essential to support fetal and uterine growth.
9
Thureen, Patti J., Susan M. Anderson, and William W. Hay. "Regulation of uterine and umbilical amino acid uptakes by maternal amino acid concentrations." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 279, no. 3 (September 1, 2000): R849—R859. http://dx.doi.org/10.1152/ajpregu.2000.279.3.r849.
Анотація:
We tested the hypothesis that decreased fetal amino acid (AA) supply, produced by maternal hypoaminoacidemia (low AA) during hyperglycemia (HG), is reversible with maternal AA infusion and regulates fetal insulin concentration ([I]). We measured net uterine and umbilical AA uptakes during maternal HG/low AA concentration ([AA]) and after maternal intravenous infusion of a mixed AA solution. After 5 days HG, all maternal [AA] except glycine were decreased >50%, particularly essential [AA] ( P < 0.00005). Most fetal [AA] also were decreased, especially branched-chain AA ( P < 0.001). Maternal AA infusion increased net uterine uptakes of Val, Leu, Ile, Met, and Ser and net umbilical uptakes of Val, Leu, Ile, Met, Phe, and Arg but did not change net uteroplacental uptake of any AA. Fetal [I] increased 55 ± 14%, P < 0.001, with correction of fetal [AA], despite the lack of change in fetal glucose concentration. Thus generalized maternal hypoaminoacidemia decreases uterine and umbilical uptakes of primarily the essential AA and decreases fetal branched-chain [AA]. These changes are reversed with correction of maternal [AA], which also increases fetal [I].
10
Wallace, Jacqueline M., Deirdre A. Bourke, Raymond P. Aitken, Neil Leitch, and William W. Hay. "Blood flows and nutrient uptakes in growth-restricted pregnancies induced by overnourishing adolescent sheep." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 282, no. 4 (April 1, 2002): R1027—R1036. http://dx.doi.org/10.1152/ajpregu.00465.2001.
Анотація:
To establish physiological mechanisms for fetal growth restriction in pregnant adolescent ewes we studied uterine, fetal, and uteroplacental metabolism in ewes offered a high ( n = 12) or moderate ( n = 10) dietary intake. High intakes decreased placental (226 vs. 414 g, P < 0.001) and fetal weight (3,323 vs. 4,626 g, P < 0.01). Uterine blood flow was reduced absolutely (−36%) but proportional to conceptus weight; umbilical blood flow was reduced absolutely (−37%) and per fetal weight (−15%). Uterine oxygen uptake was decreased per conceptus weight (−14%); there was no change in fetal weight oxygen consumption. Uteroplacental oxygen consumption and clearance were reduced proportional to weight. Similar changes were measured for glucose fluxes and fetal glucose concentration; fetal insulin concentration was reduced. In this model of fetal growth restriction, therefore, maintenance of fetal weight-specific glucose and oxygen consumption rates are producing relative hypoglycemia and hypoxemia. This indicates that increased fetal glucose clearance and/or insulin sensitivity may be operating as compensatory mechanisms to preserve normal fetal metabolism while fetal growth is sacrificed.
11
Frolova, Antonina I., and Kelle H. Moley. "Glucose transporters in the uterus: an analysis of tissue distribution and proposed physiological roles." REPRODUCTION 142, no. 2 (August 2011): 211–20. http://dx.doi.org/10.1530/rep-11-0114.
Анотація:
Facilitative glucose transport molecules (glucose transporters, GLUTs) are responsible for glucose transport across cellular membranes. Of the 14 family members, expression of nine has been reported in the murine uterus and seven in the human uterus. Some studies reveal that adequate glucose uptake and metabolism are essential for the proper differentiation of the uterine endometrium toward a receptive state capable of supporting embryo implantation. However, the mechanistic role of GLUTs in endometrial function remains poorly understood. This review aims to present the current knowledge about GLUT expression in the uterus and distribution among the different cell types within the endometrium. In addition, it analyzes the available data in the context of roles GLUTs may play in normal uterine physiology as well as the pathological conditions of infertility, endometrial cancer, and polycystic ovarian syndrome.
12
Nie, Li, You-bo Zhao, Dan Zhao, Yun Long, Yi Lei, Min Liu, Yi-cheng Wang, et al. "Progesterone-induced miR-152 interferes with embryonic implantation by downregulating GLUT3 in endometrial epithelium." American Journal of Physiology-Endocrinology and Metabolism 316, no. 4 (April 1, 2019): E557—E567. http://dx.doi.org/10.1152/ajpendo.00245.2018.
Анотація:
To investigate the role of progesterone-induced micro-RNA (miR)-152 in early embryonic development and implantation by regulating GLUT3 in endometrial epithelium, qRT-PCR was used to detect the expression of miR-152, GLUT1, and GLUT3 in the endometrial epithelial cells of female mice. GLUT1 and GLUT3 proteins were detected by immunohistochemical staining in the mouse endometrial epithelium. Bioinformatics prediction associated with a luciferase assay was performed to determine whether GLUT1 and GLUT3 are target genes of miR-152. Specific miR-152 mimics or inhibitors were transfected into the endometrial epithelial cells to, respectively, overexpress or downregulate miR-152. Next, the glucose concentration of uterine fluid was measured by conducting high-performance liquid chromatography in vivo, and the glucose uptake of the endometrial epithelial cells was observed using a fluorometric assay in vitro. Early embryonic development and implantation were also observed after the miR-152 mimics or inhibitors had been transfected. Embryo transfer was observed after the miR-152 mimic transfection. miR-152 was found to directly target and thereby downregulate GLUT3 expression. The expressions of both miR-152 and GLUT3 in the mouse endometrial epithelium had spatiotemporal characteristics on days 1–4 of pregnancy. miR-152 affected the glucose concentration of uterine fluid and the glucose uptake of endometrial epithelial cells. The transfection of specific miR-152 mimics led to impaired embryonic development and implantation. To conclude, in endometrial epithelial cells, progesterone-induced miR-152 downregulates GLUT3 at the posttranscriptional level to maintain a proper glucose concentration in the uterine fluid, which is necessary for early embryonic development and implantation.
13
Vaughan, O. R., M. J. De Blasio, and A. L. Fowden. "Ovine uteroplacental and fetal metabolism during and after fetal cortisol overexposure in late gestation." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 314, no. 6 (June 1, 2018): R791—R801. http://dx.doi.org/10.1152/ajpregu.00194.2017.
Анотація:
Cortisol modifies fetal metabolism in preparation for delivery, but whether preterm cortisol exposure programs persisting changes in fetoplacental metabolism remains unknown. This study infused fetal sheep with saline ( n = 36) or cortisol ( n = 27) to raise fetal plasma cortisol to normal prepartum concentrations for 5 days from day 125 of gestation (term: ≈145 days). Fetal uptake and uteroplacental metabolism of glucose, oxygen, and lactate, together with fetal hepatic glucogenic capacity, were measured on the final day of infusion or 5 days later. Cortisol reduced adrenal weight and umbilical glucose uptake during infusion but increased fetal glucose concentrations, hepatic glycogen content, and hepatic glucogenic enzyme activity (fructose-1,6-bisphosphatase and glucose-6-phosphatase) and gene expression ( PC and G6PC) compared with saline infusion. Postcortisol infusion, umbilical glucose uptake, and hepatic glucose-6-phosphatase activity remained low and high, respectively, whereas fetal glucose levels normalized and hepatic glycogen was lower with higher adrenal weights than in controls. Cortisol infusion increased the proportion of total uterine glucose uptake consumed by the uteroplacental tissues, irrespective of age. Placental tracer glucose transport capacity was also increased after, but not during, cortisol infusion, without changes in placental glucose transporter gene expression. Blood lactate concentration and Pco2 were higher, whereas pH and O2 content were lower in cortisol-infused than saline-infused fetuses, although uteroplacental metabolism and fetal uptake of oxygen and lactate were unaltered. The results suggest that preterm cortisol overexposure alters fetoplacental metabolism and adrenal function subsequently with persisting increases in uteroplacental glucose consumption at the expense of the fetal supply.
14
Boyle, D. W., G. Meschia, and R. B. Wilkening. "Metabolic adaptation of fetal hindlimb to severe, nonlethal hypoxia." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 263, no. 5 (November 1, 1992): R1130—R1135. http://dx.doi.org/10.1152/ajpregu.1992.263.5.r1130.
Анотація:
To test the hypothesis that an important aspect of the fetal response to severe, nonlethal hypoxia is a relatively large reduction in oxidative metabolism and small increase in lactate production by organs whose O2 supply is selectively reduced, net fluxes of O2, glucose, pyruvate, lactate, and CO2 derived from fetal plasma lactate carbon [(CO2)PL] were measured across the hindlimb and umbilical circulations in six sheep fetuses before and at 200-260 min of hypoxia. During hypoxia, blood lactate reached a high but steady level (15.2 +/- 2.2 vs. 1.7 +/- 0.2 mM; P < 0.001). Hypoxia was induced by reducing uterine blood flow. Limb O2 uptake and (CO2)PL decreased (P < 0.01) and lactate output increased (P < 0.05) (-83.1 +/- 13.9, -28.6 +/- 5.0, and +35.7 +/- 13.7 nmol.min-1 x g-1, respectively), while pyruvate and glucose uptakes remained similar to control. The increase in limb glycolysis was approximately 10% of the value that would compensate for the decrease in oxidative energy metabolism. The ratio of limb O2 uptake to fetus O2 uptake decreased significantly (0.247 +/- 0.029 vs. 0.447 +/- 0.036; P < 0.01). In contrast to fetal limb (CO2)PL, fetal (CO2)PL did not decrease. During severe, nonlethal hypoxia, fetal survival depends on uneven and counterbalancing organ O2 uptake and lactate metabolism.
15
Teng, Cecilia C., Susan Tjoa, Paul V. Fennessey, Randall B. Wilkening, and Frederick C. Battaglia. "Transplacental Carbohydrate and Sugar Alcohol Concentrations and Their Uptakes in Ovine Pregnancy." Experimental Biology and Medicine 227, no. 3 (March 2002): 189–95. http://dx.doi.org/10.1177/153537020222700306.
Анотація:
The concentrations of glucose, fructose, sorbitol, glycerol, and myo-inositol in sheep blood and tissues have been reported previously (1–5). However, the other polyols that are at low concentrations have not been investigated in pregnant sheep due to technical difficulties. By using HPLC and gas chromatography-mass spectrometry, seven polyols (myo-inositol, glycerol, erythritol, arabitol, sorbitol, ribitol, and mannitol) and three hexoses (mannose, glucose, and fructose) were identified and quantified in four blood vessels supplying and draining the placenta (maternal artery, uterine vein, fetal artery, and umbilical vein). Uterine and umbilical blood flows were measured, and uptakes of all the polyols and hexoses in both maternal and fetal circulations were calculated. There was a significant net placental release of sorbitol to both maternal and fetal circulations. Fructose was also taken up significantly by the uterine circulation. Maternal plasma mannose concentrations were higher than fetal concentrations, and there was a net umbilical uptake of mannose, characteristics that are similar to those of glucose. Myo-inositol and erythritol had relatively high concentrations in fetal plasma (697.8 ± 53 μM and 463.8 ± 27 μM, respectively). The ratios of fetal/maternal plasma arterial concentrations were very high for most polyols. The concentrations of myo-inositol, glycerol, and sorbitol were also high in sheep placental tissue (2489 ± 125 μM/kg wet tissue, 2119 ± 193 μM/kg wet tissue, and 3910 ± 369 μM/kg wet tissue), an indication that these polyols could be made within the placenta.
16
Reynolds, L. P., C. L. Ferrell, J. A. Nienaber, and S. P. Ford. "Effects of chronic environmental heat stress on blood flow and nutrient uptake of the gravid bovine uterus and foetus." Journal of Agricultural Science 104, no. 2 (April 1985): 289–97. http://dx.doi.org/10.1017/s002185960004394x.
Анотація:
SummaryTo evaluate the effects of chronic environmental heat stress during mid-gestation on gravid uterine and foetal metabolism, mature Hereford cows were assigned to control (n = 8) or heat stress (n = 5) treatments beginning on day 100 of gestation. Uterine and umbilical blood flows were estimated by the steady-state diffusion procedure on day 169 ± 4 of gestation. Oxygen (O2), glucose, lactate, α-amino nitrogen and urea nitrogen concentrations were determined for uterine and umbilical blood samples collected during this procedure. Foetuses and foetal fluids were collected on day 174±4.Uterine and umbilical blood flows were reduced and foetal weight also was less for heat-stressed than for control cows. In addition, foetal liver weight as a proportion of foetal weight and total foetal liver RNA and protein were less for heat-stressed cows. Uterine and umbilical arterial–venous concentration differences in metabolites were similar between the two groups. Uterine, foetal and utero-placental uptake or secretion rates of the metabolites measured in this study were reduced in the heat-stressed cows, primarily because of differences in blood flow. Thus, chronic heat stress during mid-gestation had an adverse effect on foetal development resulting, at least in part, from decreased uterine and umbilical blood flows, which led to a reduction in uterine, utero-placental and foetal nutrient uptake or secretion rates.
17
Tanner, Amelia R., Asghar Ali, Quinton A. Winger, Paul J. Rozance, and Russell V. Anthony. "152 Impact of chorionic somatomammotropin RNA interference on uterine blood flow and placental glucose uptake in the absence of intrauterine growth restriction." Journal of Animal Science 98, Supplement_4 (November 3, 2020): 121. http://dx.doi.org/10.1093/jas/skaa278.220.
Анотація:
Abstract Chorionic somatomammotropin (CSH) is one of the most abundant hormones produced by the sheep placenta, yet the exact function of CSH has been elusive. Previously we reported the use of in vivo RNA interference (RNAi) to assess the impact of CSH deficiency on placental and fetal growth in sheep. Near-term (135 dGA), there are two distinct CSH RNAi phenotypes: 1) pregnancies with intrauterine growth restriction (IUGR), and 2) pregnancies with normal fetal and placental weights. This study describes physiological changes in the latter phenotype. To generate the CSH RNAi pregnancies, the trophectoderm of hatched blastocysts (9 dGA) were infected with lentiviral-constructs expressing either a scrambled control (NTS) or CSH-specific shRNA (CSH RNAi), prior to transfer into synchronized recipient ewes. At 120 dGA, 6 NTS and 6 CSH RNAi pregnancies were fitted with maternal and fetal catheters. Uterine and umbilical blood flows were measured utilizing the 3H2O transplacental diffusion technique at 132 dGA, and nutrient uptakes were calculated by the Fick principle. Resulting data were analyzed by Student’s t-test and significance was set at P ≤ 0.05. CSH RNAi tended (P ≤ 0.10) to reduce placentome weight with no effect on fetal weight. Absolute (ml/min) and relative (ml/min/kg fetus) uterine blood flows were reduced (P ≤ 0.05) in CSH RNAi pregnancies, but umbilical flows were not impacted. The uterine artery-to-vein glucose gradient (mmol/l) was significantly (P ≤ 0.05) increased, whereas the gradients for taurine and glycine were reduced (P ≤ 0.05). Uteroplacental glucose uptake (mmol/min/kg placenta) was increased 27% (P ≤ 0.05), whereas umbilical glucose uptake (mmol/min/kg fetus) was reduced 13%. This cohort demonstrates that even in the absence of IUGR, CSH deficiency has significant physiological ramifications, and the investigation of CSH RNAi pregnancies exhibiting both IUGR and non-IUGR phenotypes may help determine the direct effects of CSH and its potential impact on fetal programming. Supported by NIH R01 HD093701.
18
DiGiacomo, J. E., and W. W. Hay. "Placental-fetal glucose exchange and placental glucose consumption in pregnant sheep." American Journal of Physiology-Endocrinology and Metabolism 258, no. 2 (February 1, 1990): E360—E367. http://dx.doi.org/10.1152/ajpendo.1990.258.2.e360.
Анотація:
To determine the separate effects of changes in fetal glucose and insulin concentrations on uteroplacental glucose transfer (UPGT) and consumption (UPGC) we studied 24 late-gestation pregnant sheep during fetal insulin infusions alone and with simultaneous glucose clamp. Insulin infusion alone increased fetal glucose utilization rate (GUR) by 45% (P less than 0.001), decreasing fetal glucose concentration by 40% (P less than 0.01) and thereby increasing fetal glucose clearance (Clglu) by 150% (P less than 0.001). Maternal-fetal glucose gradient also increased, resulting in a 40% increase (P less than 0.02) in UPGT [measured as umbilical glucose uptake (UGU)] and a 30% decrease (P less than 0.05) in UPGC. Addition of a fetal glucose clamp returned fetal glucose concentration to base line and restored UPGC and UGU to control values with a further 2.25-fold increase in fetal GUR. Clglu did not change, as the increase in GUR was proportional to the increase in fetal glucose concentration. Similarly, in animals receiving an insulin infusion plus glucose clamp throughout, maternal glucose concentration, fetal glucose concentration, UPGC, and UGU did not change, whereas GUR and Clglu increased approximately 1.9-fold. These changes were noted at constant maternal glucose concentration and uterine glucose uptake. Thus variation in fetal glucose concentration rather than fetal insulin concentration directly regulates uteroplacental glucose transfer and consumption, whereas both fetal insulin and glucose affect, in separate ways, fetal glucose utilization and clearance.
19
Gardner, HG, and PL Kaye. "Characterization of glucose transport in preimplantation mouse embryos." Reproduction, Fertility and Development 7, no. 1 (1995): 41. http://dx.doi.org/10.1071/rd9950041.
Анотація:
Membrane transport of glucose divorced from metabolism, was analysed in 2-cell embryos, morulae and blastocysts in the preimplantation mouse. A non-metabolizable radiolabelled analogue, 3,0 methyl D-glucose (3OMG) was used, and glucose was used as well in morulae and blastocysts; incubation times were < or = 5 min. Uptake occurred by combination of a non-saturable process, resistant to cytochalasin-B, and a facilitated process exhibiting classic Michaelis-Menten kinetics. The rate constant for the non-saturable component increased from 1.22 +/- 0.12 pL embryo-1 min-1 in 2-cell embryos to 2.08 +/- 0.44 pL embryo-1 min-1 in blastocysts, determined using 3OMG. The Km values of the saturable component for 3OMG at 22 degrees C were relatively constant at about 6.5 mM in 2-cell embryos, morulae and blastocysts. At 37 degrees C, the Km increased from 6 mM in 2-cell embryos to 17 mM in blastocysts. Vmax increased about five-fold during development from the 2-cell stage to the morula stage and about three-fold during development to the blastocyst. The Km values for glucose in morulae and blastocysts were constant at about 1.3 mM at 37 degrees C. Uptake of 3OMG in blastocysts was inhibited by glucose and stimulated by incubation in glucose-free medium. There was no kinetic evidence for the participation of multiple saturable components in uptake by blastocysts or morulae. This supports the observation that the glucose transporter GLUT2, which is first expressed at the 8-cell stage to supplement GLUT1 expressed in the oocyte, does not contribute to the uptake of environmental glucose and is, therefore, probably restricted in expression to abcoelic membrane areas of the trophectoderm. Together with the known values of glucose in uterine fluid, the kinetic data indicate that most glucose enters the trophectoderm by this GLUT1 at a rate which directly reflects the external glucose concentrations. The activity increased on a cellular basis as development proceeded, suggesting increased activity to meet the increasing metabolic requirements of the blastocyst for glucose.
20
Shida, M., M. Murakami, H. Tsukada, Y. Ishiguro, K. Kikuchi, E. Yamashita, H. Kajiwara, M. Yasuda, and M. Ide. "F-18 fluorodeoxyglucose uptake in leiomyomatous uterus." International Journal of Gynecologic Cancer 17, no. 1 (January 2007): 285–90. http://dx.doi.org/10.1111/j.1525-1438.2006.00778.x.
Анотація:
Leiomyomas of uterus are common disease in gynecology. It is important to differentiate leiomyoma from leiomyosarcoma at the decision of treatment methods, especially in the case of the conservative treatment for uterine leiomyoma. But the exact diagnosis of benign leiomyoma is often difficult due to the degeneration of myoma by imaging modalities including magnetic resonance imaging. Recently, whole-body positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) has been used for a diagnosis of malignant tumors. There is a growing body of evidence for the use of FDG in differentiating malignant from benign disease. But optimal utilization in gynecology remains unclear. Our case represents increased uptake of FDG in myomatous uterus, which is pathologically confirmed benign leiomyoma by the hysterectomy. Immunohistochemical analysis of glucose transporter-1 showed positive in endometrial tissue and negative in leiomyoma. Our case indicates that myomatous uterus in premenopausal women shows the potential pitfall of a positive result of FDG-PET
21
Kitanaka, T., R. D. Gilbert, and L. D. Longo. "Maternal responses to long-term hypoxemia in sheep." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 256, no. 6 (June 1, 1989): R1340—R1347. http://dx.doi.org/10.1152/ajpregu.1989.256.6.r1340.
Анотація:
To determine the maternal cardiovascular responses to long-term hypoxemia, we studied three groups of animals: 1) pregnant ewes (n = 20) at 110-115 days gestation subjected to hypoxia for up to 28 days; 2) pregnant ewes (n = 4) that served as normoxic controls; and 3) nonpregnant ewes (n = 6) subjected to hypoxemia for up to 28 days. We measured mean arterial pressure, heart rate, uterine blood flow, and uterine vascular resistance continuously for 1 h/day while the ewe was exposed to an inspired O2 fraction of 12-13% for at least 17 days. Arterial PO2, O2 saturation, hemoglobin, arteriovenous O2 difference, and uterine O2 uptake were measured daily while blood volume and erythropoietin concentration were measured weekly. In the pregnant hypoxic group arterial PO2 decreased from a control value of 101.5 +/- 5.1 to 59.2 +/- 5.1 Torr within a few minutes, where it remained throughout the study. The hemoglobin concentration increased from 8.9 +/- 0.5 to 10.0 +/- 0.5 g/dl within 24 h where it remained, whereas erythropoietin concentration increased from 16.6 +/- 2.1 to 39.1 +/- 7.8 mU/ml at 24 h but then returned to near-control levels. Arterial glucose concentration, mean arterial pressure, and cardiac output decreased slightly but insignificantly. In contrast, body weight, heart rate, blood volume, uterine blood flow, uterine O2 flow, uteroplacental O2 uptake, and the concentrations of catecholamines and cortisol remained relatively constant. Thus both pregnant and nonpregnant sheep experience relatively minor cardiovascular and hematologic responses in response to long-term hypoxemia of moderate severity.
22
Frolova, Antonina I., and Kelle H. Moley. "Quantitative Analysis of Glucose Transporter mRNAs in Endometrial Stromal Cells Reveals Critical Role of GLUT1 in Uterine Receptivity." Endocrinology 152, no. 5 (February 22, 2011): 2123–28. http://dx.doi.org/10.1210/en.2010-1266.
Анотація:
Recurrent miscarriages affect about 1–2% of couples trying to conceive; however, mechanisms leading to this complication are largely unknown. Most studies focus on the early embryo, but proper development and implantation of the blastocyst are also dependent on optimal endometrial progression into a receptive state. One of the key steps in the uterine preparation for embryo receptivity, known as decidualization, is the differentiation of endometrial stromal cells (ESCs) into decidual cells. During this transition, the ESCs undergo a drastic change in glucose metabolism. The efficiency of glucose uptake is determined by a family of facilitative glucose transporters (GLUTs), and many have been identified in the stroma. The primary focus of this work was to quantify the absolute amount of GLUT mRNAs in this cell type before and after decidualization. We used primary ESCs isolated from murine and human uteri. We developed and validated cDNA-based calibration curves for each GLUT and used these primers to arrive at absolute mRNA copy numbers. Here, we report all the GLUT mRNAs that are present in the ESCs and their abundance under both conditions, control and decidualized. GLUT1 mRNA is the most abundant and critical transporter in ESCs of both species, because knocking down this GLUT with sort hairpin RNA leads to dramatically reduced decidualization. These findings suggest that GLUT1 mRNA expression is essential for decidualization and we are the first to determine a possible mechanism to explain how maternal conditions of abnormal glucose utilization may impair implantation at the level of the ESCs.
23
Bertolini, M., A. L. Moyer, J. B. Mason, C. A. Batchelder, K. A. Hoffert, L. R. Bertolini, G. F. Carneiro, et al. "Evidence of increased substrate availability to in vitro-derived bovine foetuses and association with accelerated conceptus growth." Reproduction 128, no. 3 (September 2004): 341–54. http://dx.doi.org/10.1530/rep.1.00188.
Анотація:
Changes in placental development have been associated with foetal abnormalities after in vitro embryo manipulations. This study was designed to investigate bovine conceptus development and substrate levels in plasma and fluids in in vivo- and in vitro-produced (IVP) concepti and neonates. In vivo-produced and IVP embryos were derived by established embryo production procedures. Pregnant animals from both groups were slaughtered on days 90 or 180 of gestation, or allowed to go to term. Conceptus and neonatal physical traits were recorded; foetal, maternal and neonatal blood, and foetal fluids were collected for the determination of blood and fluid chemistry, and glucose, fructose and lactate concentrations. Placental transcripts for specific glucose transporters were determined by quantitative RT-PCR. No significant differences in uterine and conceptus traits were observed between groups on day 90. On day 180, larger uterine, placental and foetal weights, and an increase in placental gross surface area (SA) in IVP pregnancies were associated with increased glucose and fructose accumulation in foetal plasma and associated fluids, with no differences in the expression of components of the glucose transporter system. Therefore, the enlarged placental SA in IVP pregnancies suggests an increase in substrate uptake and transport capacity. Newborn IVP calves displayed higher birth weights and plasma fructose concentrations soon after birth, findings which appeared to be associated with clinical and metabolic distress. Our results indicated larger concepti and increased placental fructogenic capacity in mid- to late IVP pregnancies, features which appeared to be associated with an enhanced substrate supply, potentially glucose, to the conceptus.
24
Fowden, Abigail L., and Alison J. Forhead. "Insulin Deficiency Alters the Metabolic and Endocrine Responses to Undernutrition in Fetal Sheep Near Term." Endocrinology 153, no. 8 (June 5, 2012): 4008–18. http://dx.doi.org/10.1210/en.2012-1063.
Анотація:
Insulin deficiency affects the adult metabolic response to undernutrition, but its effects on the fetal response to maternal undernutrition remain unknown. This study examined the effects of maternal fasting for 48 h in late gestation on the metabolism of fetal sheep made insulin deficient by pancreatectomy (PX). The endocrine and metabolic responses to maternal fasting differed between intact, sham-operated and PX fetuses, despite a similar degree of hypoglycemia. Compared with intact fetuses, there was no increase in the plasma concentrations of cortisol or norepinephrine in PX fetuses during maternal fasting. In contrast, there was a significant fasting-induced rise in plasma epinephrine concentrations in PX but not intact fetuses. Umbilical glucose uptake decreased to a similar extent in both groups of fasted animals but was associated with a significant fall in glucose carbon oxidation only in intact fetuses. Pancreatectomized but not intact fetuses lowered their oxygen consumption rate by 15–20% during maternal fasting in association with increased uteroplacental oxygen consumption. Distribution of uterine oxygen uptake between the uteroplacental and fetal tissues therefore differed with fasting only in PX fetuses. Both groups of fetuses produced glucose endogenously after maternal fasting for 48 h, which prevented any significant fall in the rate of fetal glucose utilization. In intact but not PX fetuses, fasting-induced glucogenesis was accompanied by a lower hepatic glycogen content. Chronic insulin deficiency in fetal sheep therefore leads to changes in the counterregulatory endocrine response to hypoglycemia and an altered metabolic strategy in dealing with nutrient restriction in utero.
25
Symonds, M. E., M. J. Bryant, D. A. L. Shepherd, and M. A. Lomax. "Glucose metabolism in shorn and unshorn pregnant sheep." British Journal of Nutrition 60, no. 2 (September 1988): 249–63. http://dx.doi.org/10.1079/bjn19880097.
Анотація:
1. Whole-body, hind-limb and uterine tissue metabolism of glucose was studied using a combination of isotopic and arterio-venous difference techniques in shorn and unshorn pregnant sheep over the final 4 weeks of pregnancy. This was combined with the measurement of the concentrations of oxygen and carbon dioxide in arterial blood and plasma concentrations of lactate, acetate, non-esterified fatty acids, 3-hydroxybutyrate, glycerol, growth hormone (GH), insulin, glucagon, cortisol, thyroxine and 3, 5, 3'-triiodothyronine (T3).2. Glucose entry rate was 28 % higher in shorn ewes compared with unshorn controls, even though there was no difference in the arterial plasma concentration of glucose. This effect may have been caused by a decrease in the molar rate, insulin: glucagon (I:G), which was 40% lower in shorn ewes as a result of a significant decrease in the plasma concentration of insulin. There was no difference in the plasma concentration of cortisol or GH.3. Blood flow across the hind-limb or uterine tissues was not significantly different between shorn and unshorn groups, neither were the net glucose uptake, glucose oxidation rate or contribution of glucose to O2 consumption across these tissues.4. Insulin-tolerance tests performed on a separate group of shorn and unshorn ewes showed an increased sensitivity to the hypoglycaemic effects of insulin in the shorn group.5. There was no significant difference between shorn and unshorn animals in the contribution of glucose to CO2 output or in the proportion of glucose entry rate oxidized. CO2 entry rate was 18% higher in shorn ewes compared with unshorn controls which resulted in a 26 % higher estimated value for heat production. There was a 47 % increase in glucose oxidation rate in shorn ewes but there was no significant difference in the proportion of total heat production which was derived from glucose. The arterial concentrations of O2 and CO2 were significantly higher in shorn ewes, which may be an indication of the higher metabolic rate in these animals. This effect may be mediated via a significant rise in plasma T3 concentration in the shorn group.6. It is concluded that as a result of long-term cold exposure there is a significant increase in whole-body glucose entry and oxidation rates in the shorn pregnant ewe. The increase in insulin sensitivity at the same time as a decrease in plasma insulin concentration may represent a mechanism to ensure continued glucose supply to insulinsensitive tissues while the concomitant decrease in plasma I:G stimulates hepatic gluconeogenesis.
26
GATFORD, Kathryn L., E. Marelyn WINTOUR, Miles J. DE BLASIO, Julie A. OWENS, and Miodrag DODIC. "Differential timing for programming of glucose homoeostasis, sensitivity to insulin and blood pressure by in utero exposure to dexamethasone in sheep." Clinical Science 98, no. 5 (April 3, 2000): 553–60. http://dx.doi.org/10.1042/cs0980553.
Анотація:
Numerous epidemiological studies have related an increased risk of adult-onset cardiovascular and metabolic disease to an adverse intra-uterine environment at critical periods. We have shown that fetal sheep exposed to dexamethasone for only 2 days at 27 days of gestation (term ≈ 150 days) became hypertensive adults, whereas those exposed at 64 days of gestation remained normotensive, as did controls. In the same sheep, now nearly 5 years old, we performed glucose tolerance tests and hyperinsulinaemic euglycaemic clamps to study the insulin sensitivity of glucose, amino acid and non-esterified fatty acid metabolism. Glucose tolerance, calculated as the area under the curve, after intravenous administration of bolus glucose and insulin secretion in response to a glucose challenge were not altered in any group. There were no significant differences in the insulin sensitivity of net whole-body glucose or amino acid uptake. However, suppression of lipolysis by insulin, measured as the proportional decrease in the circulating concentration of non-esterified fatty acids during the hyperinsulinaemic clamp, was 69±1.2% at steady-state plasma insulin levels (≈ 1000 m-units/l) in the group exposed to dexamethasone at 27 days of gestation, but only 50.8±6.5% in the controls (P < 0.05). In the group exposed to dexamethasone at 64 days of gestation, the decrease was 66.4±5.1%, which did not reach significance compared with the controls (P = 0.10). Thus brief dexamethasone exposure during early gestation programmed hypertension independently of insulin resistance of glucose or amino acid metabolism; however, it did lead to increased insulin sensitivity of the inhibition of lipolysis, which may increase susceptibility to the development of obesity postnatally.
27
Ak, ??lknur, Sinan ??zalp, ??mer T. Yal??in, Evren Zor, and Erkan Vardareli. "Uptake of 2-[18F]fluoro-2-deoxy-D-glucose in uterine leiomyoma: imaging of four patients by coincidence positron emission tomography." Nuclear Medicine Communications 25, no. 9 (September 2004): 941–45. http://dx.doi.org/10.1097/00006231-200409000-00012.
28
Kua, Kok Lim, Shanming Hu, Chunlin Wang, Jianrong Yao, Diana Dang, Alexander B. Sawatzke, Jeffrey L. Segar, Kai Wang, and Andrew W. Norris. "Fetal hyperglycemia acutely induces persistent insulin resistance in skeletal muscle." Journal of Endocrinology 242, no. 1 (July 2019): M1—M15. http://dx.doi.org/10.1530/joe-18-0455.
Анотація:
Offspring exposed in utero to maternal diabetes exhibit long-lasting insulin resistance, though the initiating mechanisms have received minimal experimental attention. Herein, we show that rat fetuses develop insulin resistance after only 2-day continuous exposure to isolated hyperglycemia starting on gestational day 18. Hyperglycemia-induced reductions in insulin-induced AKT phosphorylation localized primarily to fetal skeletal muscle. The skeletal muscle of hyperglycemia-exposed fetuses also exhibited impaired in vivo glucose uptake. To address longer term impacts of this short hyperglycemic exposure, neonates were cross-fostered and examined at 21 days postnatal age. Offspring formerly exposed to 2 days late gestation hyperglycemia exhibited mild glucose intolerance with insulin signaling defects localized only to skeletal muscle. Fetal hyperglycemic exposure has downstream consequences which include hyperinsulinemia and relative uteroplacental insufficiency. To determine whether these accounted for induction of insulin resistance, we examined fetuses exposed to late gestational isolated hyperinsulinemia or uterine artery ligation. Importantly, 2 days of fetal hyperinsulinemia did not impair insulin signaling in murine fetal tissues and 21-day-old offspring exposed to fetal hyperinsulinemia had normal glucose tolerance. Similarly, fetal exposure to 2-day uteroplacental insufficiency did not perturb insulin-stimulated AKT phosphorylation in fetal rats. We conclude that fetal exposure to hyperglycemia acutely produces insulin resistance. As hyperinsulinemia and placental insufficiency have no such impact, this occurs likely via direct tissue effects of hyperglycemia. Furthermore, these findings show that skeletal muscle is uniquely susceptible to immediate and persistent insulin resistance induced by hyperglycemia.
29
Sadowska, Joanna, Wioleta Dudzińska, and Izabela Dziaduch. "Effects of different models of sucrose intake on the oxidative status of the uterus and ovary of rats." PLOS ONE 16, no. 5 (May 18, 2021): e0251789. http://dx.doi.org/10.1371/journal.pone.0251789.
Анотація:
The aim of the study was to assess the effect of different models of sucrose intake on carbohydrate-lipid metabolism and changes in oxidant balance in the ovaries and uterus of rats. Animals were divided into three groups: I—basic feed, II—feed contains 8% of sucrose, III—alternately every second week the basic feed and modified feed contains 16% of sucrose. The diet containing 8% of sucrose was found to result in an increased activity of antioxidant enzymes in the blood, with unchanged malonylodialdehyde concentration. Variable sucrose administration pattern intensified oxidative stress in the blood and led to disturbed redox equilibrium in the rat uterus, even at a comparable long-term sucrose uptake as in the group II. This was manifested as a reduced superoxide dismutase activity (in the blood and uterus) and a higher malonylodialdehyde concentration (in the uterus). The changes observed could have been a result of metabolic disorders (higher amount of visceral fat, higher glucose concentration, higher index of homeostasis model assessment of insulin resistance, and reduced HDL-cholesterol concentration) and endocrine disorders (higher oestrogen concentrations). Changes in the antioxidant status in the rats kept on the alternating diet, may underpin the failure of fertilised egg implantation in the uterine tissue and pregnancy completion.
30
Shuch, Brian, Kevin P. Asher, Clara Chen, Kelly Lin, Gennady Bratslavsky, W. Marston Linehan, and Ramaprasad Srinivasan. "Clinical evaluation of 2-(18F) fluoro-2 deoxy-D-glucose PET/ CT in hereditary leiomyomatosis and renal cell carcinoma." Journal of Clinical Oncology 31, no. 6_suppl (February 20, 2013): 383. http://dx.doi.org/10.1200/jco.2013.31.6_suppl.383.
Анотація:
383 Background: 2-(18F) fluoro-2 deoxy-D-glucose (FDG) PET/CT is a useful tool in the staging of malignancies. In patients with kidney cancer, the role of FDG is limited in those with clear-cell histology and remains to be evaluated with other subtypes. Kidney cancer associated with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is characterized by a defect in the Krebs cycle rendering these tumors highly dependent on aerobic glycolysis (the ‘Warburg effect’) with high glucose uptake to fulfill their energy requirements; we hypothesized that FDG PET/CT may have excellent sensitivity for staging in this condition. Methods: We retrospectively reviewed patients with HLRCC kidney cancer that underwent FDG PET/CT in conjunction with anatomic imaging at our institution. The ability of FDG PET/CT to detect malignant lesions (defined using pathologic or radiologic criteria) was evaluated. Results: A total of 30 patients underwent 42 PET /CTs. Conventional imaging identified a total of 107 lesions. Both patient and lesion-based analyses were performed. A total of 90 lesions, including ten renal lesions, were classified as malignant. 76 of 80 extra-renal lesions were correctly identified as malignant by PET/CT (sensitivity, 95%, CI 88-98%). In contrast, only 4 of 10 renal lesions were correctly identified as malignant (sensitivity, 40%, CI 17-69%). 11 of 12 histologically confirmed extra-renal lesions were PET avid (sensitivity, 92%, CI-64-98%). 10 of 12 (83%) benign lesions associated with HLRCC including uterine/cutaneous leiomyomas and adrenal nodules were PET avid. In a patient based analysis, all 18 patients with extra-renal spread of kidney cancer were correctly identified (sensitivity 100%, CI 82-100%). Conclusions: FDG PET/CT is a highly sensitive diagnostic modality for identifying metastatic kidney cancer associated with HLRCC. Prospective studies evaluating the utility of PET/CT imaging to characterize response to systemic therapy are currently underway.
31
La Rosa, Federica, Letizia Guiducci, Maria Angela Guzzardi, Andrea Cacciato Insilla, Silvia Burchielli, Maurizia Rossana Brunetto, Ferruccio Bonino, Daniela Campani, and Patricia Iozzo. "Maternal High-Fat Feeding Affects the Liver and Thymus Metabolic Axis in the Offspring and Some Effects Are Attenuated by Maternal Diet Normalization in a Minipig Model." Metabolites 11, no. 12 (November 26, 2021): 800. http://dx.doi.org/10.3390/metabo11120800.
Анотація:
Maternal high-fat diet (HFD) affects metabolic and immune development. We aimed to characterize the effects of maternal HFD, and the subsequent diet-normalization of the mothers during a second pregnancy, on the liver and thymus metabolism in their offspring, in minipigs. Offspring born to high-fat (HFD) and normal diet (ND) fed mothers were studied at week 1 and months 1, 6, 12 of life. Liver and thymus glucose uptake (GU) was measured with positron emission tomography during hyperinsulinemic-isoglycemia. Histological analyses were performed to quantify liver steatosis, inflammation, and hepatic hematopoietic niches (HHN), and thymocyte size and density in a subset. The protocol was repeated after maternal-diet-normalization in the HFD group. At one week, HFDoff were characterized by hyperglycemia, hyperinsulinemia, severe insulin resistance (IR), and high liver and thymus GU, associating with thymocyte size and density, with elevated weight-gain, liver IR, and steatosis in the first 6 months of life. Maternal diet normalization reversed thymus and liver hypermetabolism, and increased HHN at one week. It also normalized systemic insulin-sensitivity and liver fat content at all ages. Instead, weight-gain excess, hyperglycemia, and hepatic IR were still observed at 1 month, i.e., end-lactation. We conclude that intra-uterine HFD exposure leads to time-changing metabolic and immune-correlated abnormalities. Maternal diet-normalization reversed most of the effects in the offspring.
32
Omar, Asma, Lance Li Puma, Briana Risk, Aria Witt, Cheyanne Izon, Luke Whitcomb, Dorcas Kareng, Gerrit Bouma, Quinton Winger, and Adam Chicco. "Impact of Maternal Omega-3 Fatty Acid Intake on Ovine Placental and Fetal Tissue Metabolism." Current Developments in Nutrition 6, Supplement_1 (June 2022): 698. http://dx.doi.org/10.1093/cdn/nzac061.082.
Анотація:
Abstract Objectives Dietary supplementation of omega-3 fatty acids such as docosahexaenoic acid (DHA) during pregnancy is often recommended to support optimal fetal brain development and cognitive function of the offspring. DHA supplementation also influences cardiometabolic risk parameters in adults, but its effect on fetal metabolism and subsequent risk is poorly understood. The aim of this study was to determine the effects of maternal DHA supplementation (MDS) on placental and fetal nutrient handling during pregnancy. Methods White-faced ewes were fed either a control diet (Show-rite NewCo Lamb Feed) or a DHA-supplemented diet (control diet + 3% w/w algae-derived DHA) from 2–3 weeks before pregnancy until mid-gestation (75 days), after which a C-section was performed to collect the placenta and fetal tissues for metabolic analyses. Results MDS significantly increased serum DHA levels and decreased serum triglycerides in the uterine (maternal) circulation, but not umbilical (fetal) circulation. Nevertheless, MDS resulted in significant DHA enrichment of the placenta and all fetal tissues examined, and differentially affected the protein expression of the four major fatty acid transport proteins FATP1, FATP4, CD36 and FABP in placenta, muscle, liver and heart, but had no effect on kidney or brain. Consistent with these findings, MDS tended to increase the capacity for fat over pyruvate oxidation in fetal muscle and heart, but favored a greater capacity for glucose uptake and oxidation in fetal liver. Conclusions This study is the first to validate use of an ovine model for investigating the impact of maternal DHA supplementation on fetal metabolism and development. Results demonstrate a complex tissue-specific effect of MDS on fetal tissue carbohydrate and fatty acid metabolism that favors a greater capacity for serum glucose disposal and fatty acid oxidation. Whether these changes ultimately impact nutrient metabolism and cardiometabolic risk in the offspring later in life merits further investigation. Funding Sources Colorado Agricultural Experiment Station.
33
Boyle, D. W., S. Lecklitner, and E. A. Liechty. "Effect of prolonged uterine blood flow reduction on fetal growth in sheep." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 270, no. 1 (January 1, 1996): R246—R253. http://dx.doi.org/10.1152/ajpregu.1996.270.1.r246.
Анотація:
The purpose of the present investigation was to study the effect of 7 days of uterine blood flow reduction on fetal growth. Reduction in uterine blood flow was accomplished by external occlusion of the terminal aorta in 20 pregnant sheep. Linear growth was monitored daily by means of a crown-rump length measuring device. The deliveries of oxygen, glucose, and lactate to the fetus, as well as their uptakes by the fetus, were determined before and after 7 days of uterine blood flow reduction and correlated with rates of fetal growth. Identical studies were conducted in nine control animals. Uterine blood flow reduction resulted in a significant decrease in fetal oxygen delivery and fetal arterial oxygen content. Linear growth rate decreased by 38% in the occluded animals during hypoxemia. In addition, there was a 20% reduction in daily weight gain in occluded animals compared with controls. There were no differences in the uptakes of oxygen, glucose, and lactate by the fetus. Positive correlations were found between linear growth rate and fetal arterial oxygen content (r2 = 0.25, P = 0.0001) and between linear growth rate and fetal oxygen delivery (r2 = 0.21, P = 0.0006). The correlations between linear growth rate and fetal oxygenation provide strong evidence of the central role of oxygen in the regulation of fetal growth.
34
Molina, R. D., G. Meschia, and R. B. Wilkening. "Uterine Blood Flow, Oxygen and Glucose Uptakes at Mid-Gestation in the Sheep." Experimental Biology and Medicine 195, no. 3 (December 1, 1990): 379–85. http://dx.doi.org/10.3181/00379727-195-43158aa.
35
Barry, T. N., and T. R. Manley. "Glucose and protein metabolism during late pregnancy in triplet-bearing ewes given fresh forages ad lib." British Journal of Nutrition 54, no. 2 (September 1985): 521–33. http://dx.doi.org/10.1079/bjn19850137.
Анотація:
1. Ewes of the Booroola x Romney genotype carrying triplet lambs were given fresh forages ad lib. in late pregnancy. In Expt 1, groups of three ewes were given kale (Brassica oleracea), perennial ryegrass (Loliumperenne) or perennial ryegrass (0.75)–barley (0.25). In Expt 2, groups of two or three ewes were given fresh perennial ryegrass and infused into the abomasum with iso-energetic quantities of casein and glucose in a 2 x 2 factorial arrangement. Post-lambing ewe live weights were 40–50 kg. Glucose irreversible loss (GIL) was determined from dilution of D-[U-14C]glucose.2. For ewes given kale, perennial ryegrass and perennial ryegrass—barley in Expt 1, mean metabolizable energy (ME) intakes were 0.50, 0.82 and 0.83 MJ/kg live Weight0.75 per d, GIL was 112, 142 and 157 g/d, and mean birth weight 2.22, 3.05 and 2.95 kg/lamb.3. In Expt 2, infusion of glucose, casein, and glucose+casein depressed herbage ME intake respectively by 1.6, 0.9 and 0.3 times the amount of ME infused. GIL (185–325 g/d) was increased by 800 and 350 g respectively for each kg of glucose or casein infused. Casein infusion increased calculated amino acid absorption from 0.18 to 0.36 of ME, increased wool growth and increased calculated maternal N balance. Birth weight was unaffected by nutritional treatment and averaged 3.29 kg/lamb.4. When values from both experiments were combined, birth weight was related to GIL by a hyperbolic relation, with maximum predicted birth weight being 4.1 kg/lamb. It was postulated that this value was never attained in practice, due to uterine expansion being restricted by the low maternal body size. Marked decreases in birth weight occurred when GIL decreased below 173 g/d.5. It was calculated that ewes in all treatment groups were in negative energy balance, and that glucose supplied by the kale and unsupplemented ryegrass diets were respectively below and equal to calculated conceptus uptakes of glucose necessary to maintain growth of triplet fetuses. It was further calculated that amino acid requirements of triplet-bearing ewes in late pregnancy were likely to exceed substantially net absorption from digestion of fresh forage diets, and that maternal tissues go into negative N balance to ensure fetal growth, thus explaining the lack of response to abomasal casein infusion.
36
Anthony, Russell V., Amelia R. Tanner, Cameron S. Lynch, Victoria C. Kennedy, Paul J. Rozance, and Quinton A. Winger. "264 Using in vivo RNA Interference to Investigate Ruminant Placental Function." Journal of Animal Science 99, Supplement_3 (October 8, 2021): 133. http://dx.doi.org/10.1093/jas/skab235.243.
Анотація:
Abstract Pregnant sheep have been used extensively for investigating pregnancy physiology, providing valuable information about the progression of ruminant pregnancy. The ability to place indwelling catheters, within both maternal and fetal vessels, allows for steady-state investigation of blood flow, nutrient uptakes and utilization, and hormone secretion, under non-stressed and non-anesthetized conditions. As such, our understanding of the in vivo physiology of pregnancy in sheep is unrivalled by any other species. However, until recently, a significant deficit existed in determining the specific function or significance of individual genes expressed by the placenta in livestock. To that end, we developed and have been using in vivo RNA interference (RNAi) within the sheep placenta to examine the function and relative importance of genes involved in conceptus development (PRR15 and LIN28), placental nutrient transport (SLC2A1 and SLC2A3), and placenta derived hormones (CSH). The lentiviral vector LL3.7 is used to generate virus that is stably integrated into the infected cell’s genome, thereby expressing a short-hairpin RNA (shRNA), that when processed within the cell, combines with the RNA Induced Silencing Complex (RISC) resulting in specific mRNA degradation or translational blockage. To accomplish in vivo RNAi, day 9 hatched and fully expanded blastocysts are infected with the lentivirus for 4–5 hours, and then surgically transferred to synchronized recipient uteri. Only the trophectoderm cells are infected by the replication deficient virus, leaving the inner cell mass unaltered, and we typically obtain 70–80% pregnancy rates following transfer of a single blastocyst. Data will be presented from two projects. One is focused on generating a deficiency in placental glucose transporters at mid-gestation, and the other on the impact of CSH RNAi during late gestation, demonstrating the utility of this experimental approach for examining gene function within the placenta of livestock. Supported by NIH-NICHD grants HD093701 and HD094952.
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Tanner, Amelia R., Cameron S. Lynch, Asghar Ali, Quinton A. Winger, Paul J. Rozance, and Russell V. Anthony. "IMPACT OF CHORIONIC SOMATOMAMMOTROPIN RNA INTERFERENCE ON UTERINE BLOOD FLOW AND PLACENTAL GLUCOSE UPTAKE IN THE ABSENCE OF INTRAUTERINE GROWTH RESTRICTION." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, November 4, 2020. http://dx.doi.org/10.1152/ajpregu.00223.2020.
Анотація:
Chorionic Somatomammotropin (CSH) is one of the most abundantly produced placental hormones, yet its exact function remains elusive. Near-term (135 dGA), CSH RNA interference (RNAi) results in two distinct phenotypes: 1) pregnancies with intrauterine growth restriction (IUGR), and 2) pregnancies with normal fetal and placental weights. Here we report the physiological changes in CSH RNAi pregnancies without IUGR. The trophectoderm of hatched blastocysts (9 dGA) were infected with lentiviral-constructs expressing either a scrambled control (Control RNAi) or CSH-specific shRNA (CSH RNAi), prior to transfer into synchronized recipient ewes. At 126 dGA, Control RNAi (n = 6) and CSH RNAi (n = 6) pregnancies were fitted with maternal and fetal catheters. Uterine and umbilical blood flows were measured at 132 dGA and nutrient uptakes were calculated by the Fick principle. Control RNAi and CSH RNAi pregnancies were compared by analysis of variance, and significance was set at P ≤ 0.05. Absolute (ml/min) and relative (ml/min/kg fetus) uterine blood flows were reduced (P ≤ 0.05) in CSH RNAi pregnancies, but umbilical flows were not impacted. The uterine artery-to-vein glucose gradient (mmol/l) was significantly (P ≤ 0.05) increased. The uteroplacental glucose uptake (μmol/min/kg placenta) was increased (P ≤ 0.05), whereas umbilical glucose uptake (μmol/min/kg fetus) was reduced. Our results demonstrate that CSH RNAi has significant physiological ramifications, even in the absence of IUGR, and comparing CSH RNAi pregnancies exhibiting both IUGR and non-IUGR phenotypes may help determine the direct effects of CSH and its potential impact on fetal development.
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Long, Yun, Yi-cheng Wang, Dong-zhi Yuan, Xin-hua Dai, Lin-chuan Liao, Xue-qin Zhang, Li-xue Zhang, et al. "GLUT4 in Mouse Endometrial Epithelium: Roles in Embryonic Development and Implantation." Frontiers in Physiology 12 (June 25, 2021). http://dx.doi.org/10.3389/fphys.2021.674924.
Анотація:
GLUT4 is involved in rapid glucose uptake among various kinds of cells to contribute to glucose homeostasis. Prior data have reported that aberrant glucose metabolism by GLUT4 dysfunction in the uterus could be responsible for infertility and increased miscarriage. However, the expression and precise functions of GLUT4 in the endometrium under physiological conditions remain unknown or controversial. In this study, we observed that GLUT4 exhibits a spatiotemporal expression in mouse uterus on pregnant days 1–4; its expression especially increased on pregnant day 4 during the window of implantation. We also determined that estrogen, in conjunction with progesterone, promotes the expression of GLUT4 in the endometrial epithelium in vivo or in vitro. GLUT4 is an important transporter that mediates glucose transport in endometrial epithelial cells (EECs) in vitro or in vivo. In vitro, glucose uptake decreased in mouse EECs when the cells were treated with GLUT4 small interfering RNA (siRNA). In vivo, the injection of GLUT4-siRNA into one side of the mouse uterine horns resulted in an increased glucose concentration in the uterine fluid on pregnant day 4, although it was still lower than in blood, and impaired endometrial receptivity by inhibiting pinopode formation and the expressions of leukemia inhibitory factor (LIF) and integrin ανβ3, finally affecting embryonic development and implantation. Overall, the obtained results indicate that GLUT4 in the endometrial epithelium affects embryo development by altering glucose concentration in the uterine fluid. It can also affect implantation by impairing endometrial receptivity due to dysfunction of GLUT4.
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Holmlund, Hayden, Álvaro Marín-Hernández, and Jennifer R. Chase. "Estradiol and progesterone affect enzymes but not glucose consumption in a mink uterine cell line (GMMe)." Bioscience Reports 40, no. 4 (April 2020). http://dx.doi.org/10.1042/bsr20193512.
Анотація:
Abstract Cells lining the uterus are responsible for storage and secretion of carbohydrates to support early embryonic development. Histotrophic secretions contain glycogen and glycolytic products such as lactate and pyruvate. Insufficient carbohydrate storage as glycogen has been correlated with infertility in women. While it is clear that changes in estrogen (17-β-estradiol (E2)) and progesterone (P4) in vivo affect the distribution of glucose in the uterine cells and secretions, the biochemical mechanism(s) by which they affect this crucial allocation is not well understood. Furthermore, in cultured uterine cells, neither E2 nor P4 affect glycogen storage without insulin present. We hypothesized that P4 and E2 alone affect the activity of glycolytic enzymes, glucose and glycolytic flux to increase glycogen storage (E2) and catabolism (P4) and increase pyruvate and lactate levels in culture. We measured the rate of glucose uptake and glycolysis in a mink immortalized epithelial cell line (GMMe) after 24-h exposure to 10 μM P4 and 10 nM E2 (pharmacologic levels) at 5 mM glucose and determined the kinetic parameters (Vmax, Km) of all enzymes. While the activities of many glycolytic enzymes in GMMe cells were shown to be decreased by E2 treatment, in contrast, glucose uptake, glycolytic flux and metabolites levels were not affected by the treatments. The cellular rationale for P4- and E2-induced decreases in the activity of enzymes may be to prime the system for other regulators such as insulin. In vivo, E2 and P4 may be necessary but not sufficient signals for uterine cycle carbohydrate allocation.
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Neff, Alison M., Jie Yu, Robert N. Taylor, Indrani C. Bagchi, and Milan K. Bagchi. "Insulin Signaling Via Progesterone-Regulated Insulin Receptor Substrate 2 is Critical for Human Uterine Decidualization." Endocrinology 161, no. 1 (November 21, 2019). http://dx.doi.org/10.1210/endocr/bqz021.
Анотація:
Abstract Decidualization, the process by which fibroblastic human endometrial stromal cells (HESC) differentiate into secretory decidual cells, is a critical event during the establishment of pregnancy. It is dependent on the steroid hormone progesterone acting through the nuclear progesterone receptor (PR). Previously, we identified insulin receptor substrate 2 (IRS2) as a factor that is directly regulated by PR during decidualization. IRS2 is an adaptor protein that functionally links receptor tyrosine kinases, such as insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R), and their downstream effectors. IRS2 expression was induced in HESC during in vitro decidualization and siRNA-mediated downregulation of IRS2 transcripts resulted in attenuation of this process. Further use of siRNAs targeted to IR or IGF1R transcripts showed that downregulation of IR, but not IGF1R, led to impaired decidualization. Loss of IRS2 transcripts in HESC suppressed phosphorylation of both ERK1/2 and AKT, downstream effectors of insulin signaling, which mediate gene expression associated with decidualization and regulate glucose uptake. Indeed, downregulation of IRS2 resulted in reduced expression and membrane localization of the glucose transporters GLUT1 and GLUT4, resulting in lowered glucose uptake during stromal decidualization. Collectively, these data suggest that the PR-regulated expression of IRS2 is necessary for proper insulin signaling for controlling gene expression and glucose utilization, which critically support the decidualization process to facilitate pregnancy. This study provides new insight into the mechanisms by which steroid hormone signaling intersects with insulin signaling in the uterus during decidualization, which has important implications for pregnancy complications associated with insulin resistance and infertility.
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Theil, Peter Kappel, Chantal Farmer, and Takele Feyera. "Review: Physiology and nutrition of late gestating and transition sows." Journal of Animal Science 100, no. 6 (June 1, 2022). http://dx.doi.org/10.1093/jas/skac176.
Анотація:
Abstract The physiology during late gestation and the transition period to lactation changes dramatically in the sow, especially during the latter period. Understanding the physiological processes and how they change dynamically as the sow approaches farrowing, nest building, giving birth to piglets, and producing colostrum is important because these processes greatly affect sow productivity. Glucose originating from assimilated starch accounts for the majority of dietary energy, and around farrowing, various organs and peripheral tissues compete for plasma glucose, which may become depleted. Indeed, physical activity increases shortly prior to farrowing, leading to glucose use by muscles. Approximately ½ to 1 d later, glucose is also needed for uterine contractions to expel the piglets and for the mammary gland to produce lactose and fat for colostrum. At farrowing, the sow appears to prioritize glucose to the mammary gland above the uterus, whereby insufficient dietary energy may compromise the farrowing process. At this time, energy metabolism in the uterus shifts dramatically from relying mainly on the oxidation of glucogenic energy substrates (primarily glucose) to ketogenic energy supplied from triglycerides. The rapid growth of mammary tissue occurs in the last third of gestation, and it accelerates as the sow approaches farrowing. In the last 1 to 2 wk prepartum, some fat may be produced in the mammary glands and stored to be secreted in either colostrum or transient milk. During the first 6 h after the onset of farrowing, the uptake of glucose and lactate by the mammary glands roughly doubles. Lactate is supplying approximately 15% of the glucogenic carbon taken up by the mammary glands and originates from the strong uterine contractions. Thereafter, the mammary uptake of glucose and lactate declines, which suggests that the amount of colostrum secreted starts to decrease at that time. Optimal nutrition of sows during late gestation and the transition period should focus on mammary development, farrowing performance, and colostrum production. The birth weight of piglets seems to be only slightly responsive to maternal nutrition in gilts; on the other hand, sows will counterbalance insufficient feed or nutrient intake by increasing mobilization of their body reserves. Ensuring sufficient energy to sows around farrowing is crucial and may be achieved via adequate feed supply, at least three daily meals, high dietary fiber content, and extra supplementation of energy.
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Tolwani, Angela, Magdalena Matusiak, Nam Bui, Erna Forgó, Sushama Varma, Lucia Baratto, Andrei Iagaru, Alexander J. Lazar, Matt van de Rijn, and Joanna Przybyl. "Prognostic relevance of the hexosamine biosynthesis pathway activation in leiomyosarcoma." npj Genomic Medicine 6, no. 1 (May 3, 2021). http://dx.doi.org/10.1038/s41525-021-00193-w.
Анотація:
AbstractMetabolic reprogramming of tumor cells and the increase of glucose uptake is one of the hallmarks of cancer. In order to identify metabolic pathways activated in leiomyosarcoma (LMS), we analyzed transcriptomic profiles of distinct subtypes of LMS in several datasets. Primary, recurrent and metastatic tumors in the subtype 2 of LMS showed consistent enrichment of genes involved in hexosamine biosynthesis pathway (HBP). We demonstrated that glutamine-fructose-6-phosphate transaminase 2 (GFPT2), the rate-limiting enzyme in HBP, is expressed on protein level in a subset of LMS and the expression of this enzyme is frequently retained in patient-matched primary and metastatic tumors. In a new independent cohort of 327 patients, we showed that GFPT2 is associated with poor outcome of uterine LMS but not extra-uterine LMS. Based on the analysis of a small group of patients studied by 18F-FDG-PET imaging, we propose that strong expression of GFPT2 in primary LMS may be associated with high metabolic activity. Our data suggest that HBP is a potential new therapeutic target in one of the subtypes of LMS.
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Ma, Qiuyan, Jacob R. Beal, Arpita Bhurke, Athilakshmi Kannan, Jie Yu, Robert N. Taylor, Indrani C. Bagchi, and Milan K. Bagchi. "Extracellular vesicles secreted by human uterine stromal cells regulate decidualization, angiogenesis, and trophoblast differentiation." Proceedings of the National Academy of Sciences 119, no. 38 (September 12, 2022). http://dx.doi.org/10.1073/pnas.2200252119.
Анотація:
In humans, the uterus undergoes a dramatic transformation to form an endometrial stroma-derived secretory tissue, termed decidua, during early pregnancy. The decidua secretes various factors that act in an autocrine/paracrine manner to promote stromal differentiation, facilitate maternal angiogenesis, and influence trophoblast differentiation and development, which are critical for the formation of a functional placenta. Here, we investigated the mechanisms by which decidual cells communicate with each other and with other cell types within the uterine milieu. We discovered that primary human endometrial stromal cells (HESCs) secrete extracellular vesicles (EVs) during decidualization and that this process is controlled by a conserved HIF2α-RAB27B pathway. Mass spectrometry revealed that the decidual EVs harbor a variety of protein cargo, including cell signaling molecules, growth modulators, metabolic regulators, and factors controlling endothelial cell expansion and remodeling. We tested the hypothesis that EVs secreted by the decidual cells mediate functional communications between various cell types within the uterus. We demonstrated that the internalization of EVs, specifically those carrying the glucose transporter 1 (GLUT1), promotes glucose uptake in recipient HESCs, supporting and advancing the decidualization program. Additionally, delivery of HESC-derived EVs into human endothelial cells stimulated their proliferation and led to enhanced vascular network formation. Strikingly, stromal EVs also promoted the differentiation of trophoblast stem cells into the extravillous trophoblast lineage. Collectively, these findings provide a deeper understanding of the pleiotropic roles played by EVs secreted by the decidual cells to ensure coordination of endometrial differentiation and angiogenesis with trophoblast function during the progressive phases of decidualization and placentation.
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Ji, Yun, Yuli Sun, Ning Liu, Hai Jia, Zhaolai Dai, Ying Yang, and Zhenlong Wu. "L-leucine supplementation reduces growth performance accompanied by changed profiles of plasma amino acids and expression of jejunal amino acid transporters in breast-fed intra-uterine growth-retarded piglets." British Journal of Nutrition, September 1, 2022, 1–33. http://dx.doi.org/10.1017/s0007114522002823.
Анотація:
Abstract Previously, we provided an evidence that L-leucine supplementation facilitates growth performance in suckling piglets with normal birth weight. However, it remains hitherto obscure weather breast-fed piglets displaying intrauterine growth restriction (IUGR) show a similar effect in response to L-leucine provision. In this study, seven-day-old sow-reared IUGR piglets were orally administrated with L-leucine (0, 0.7 1.4, 2.1 g/kg BW) twice daily for two weeks. Increasing leucine levels hampered the growth performance of suckling IUGR piglets. The average daily gain of IUGR piglets was significantly reduced in 1.4 g/kg BW and 2.1 g/kg BW L-leucine supplementation groups (P < 0.05). Except for ornithine and glutamine, the plasma concentrations of other amino acids were abated as L-leucine levels increased (P < 0.05). Leucine supplementation led to reduction in the levels of urea, blood ammonia, blood glucose, triglyceride, and total cholesterol, as well as an elevation in the level of low density lipoprotein cholesterol in suckling IUGR piglets (P < 0.05). In addition, 1.4g/kg BW of L-leucine enhanced the mRNA expression of ATB 0,+ , whereas decreased the mRNA abundances of CAT1, y+LAT1, ASCT2 and b 0,+ AT in the jejunum (P < 0.05). Concomitantly, the jejunum of IUGR piglets in L-leucine group contains more ATB0,+ and less SNAT2 protein than in the control (P < 0.05). Collectively, L-leucine supplementation impairs growth performance in breast-fed IUGR piglets, which may be associated with depressed nutritional conditions and alterations in the uptake of amino acids and the expression of amino acid transporters in the small intestine.
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Surov, Alexey, Stefan A. Schmidt, Vikas Prasad, Ambros J. Beer та Andreas Wienke. "FDG PET correlates weakly with HIF-1α expression in solid tumors: a meta-analysis". Acta Radiologica, 19 червня 2020, 028418512093237. http://dx.doi.org/10.1177/0284185120932378.
Анотація:
Background Hypoxia-inducible factor (HIF)-1α plays a key role in hypoxic adaptation of tumor cells. Overexpression of HIF-1α is associated with tumor aggressiveness and worse prognosis in several malignancies. Presumably, expression of HIF-1a may be reflected by positron emission tomography with 2-deoxy-2 [fluorine-18] fluoro-D-glucose (18F-FDG PET). There are inconsistent data about relationships between FDG PET and HIF-1α. Purpose To provide evident data about associations between maximum standardized uptake value (SUVmax) and HIF-1α expression in solid tumors. Material and Methods MEDLINE, SCOPUS, and EMBASE databases were screened for relationships between SUV and HIF-1α up to August 2019. Overall, 21 studies with 1154 patients were identified. The following data were extracted from the literature: authors; year of publication; number of patients; and correlation coefficients. Results Correlation coefficients between SUVmax and HIF-1α were in the range of −0.51–0.71. The pooled correlation coefficient was 0.27 (95% confidence interval [CI] = 0.14–0.41). Furthermore, correlation coefficients for some tumor entities were calculated. For this sub-analysis, data for primary tumors with >2 reports were included. The calculated correlation coefficients in the analyzed subgroups were as follows: head and neck squamous cell carcinoma: ρ = 0.25 (95% CI = 0.07–0.42); non-small lung cell cancer: ρ = 0.27 (95% CI = −0.14–0.67); uterine cervical cancer: ρ = −0.09 (95% CI = −0.89–0.71); thymic tumors: ρ = 0.39 (95% CI = 0.04–0.58). Conclusion SUVmax of FDG PET correlated weakly with expression of HIF-1α both in overall sample and tumor subgroups. Therefore, FDG PET cannot be used for prediction of hypoxia in clinical practice.
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Tanner, Amelia R., Victoria C. Kennedy, Cameron S. Lynch, Taylor K. Hord, Quinton A. Winger, Paul J. Rozance, and Russell V. Anthony. "In vivo investigation of ruminant placenta function and physiology—a review." Journal of Animal Science 100, no. 6 (June 1, 2022). http://dx.doi.org/10.1093/jas/skac045.
Анотація:
Abstract The placenta facilitates the transport of nutrients to the fetus, removal of waste products from the fetus, immune protection of the fetus and functions as an endocrine organ, thereby determining the environment for fetal growth and development. Additionally, the placenta is a highly metabolic organ in itself, utilizing a majority of the oxygen and glucose derived from maternal circulation. Consequently, optimal placental function is required for the offspring to reach its genetic potential in utero. Among ruminants, pregnant sheep have been used extensively for investigating pregnancy physiology, in part due to the ability to place indwelling catheters within both maternal and fetal vessels, allowing for steady-state investigation of blood flow, nutrient uptakes and utilization, and hormone secretion, under non-stressed and non-anesthetized conditions. This methodology has been applied to both normal and compromised pregnancies. As such, our understanding of the in vivo physiology of pregnancy in sheep is unrivalled by any other species. However, until recently, a significant deficit existed in determining the specific function or significance of individual genes expressed by the placenta in ruminants. To that end, we developed and have been using in vivo RNA interference (RNAi) within the sheep placenta to examine the function and relative importance of genes involved in conceptus development (PRR15 and LIN28), placental nutrient transport (SLC2A1 and SLC2A3), and placenta-derived hormones (CSH). A lentiviral vector is used to generate virus that is stably integrated into the infected cell’s genome, thereby expressing a short-hairpin RNA (shRNA), that when processed within the cell, combines with the RNA Induced Silencing Complex (RISC) resulting in specific mRNA degradation or translational blockage. To accomplish in vivo RNAi, day 9 hatched and fully expanded blastocysts are infected with the lentivirus for 4 to 5 h, and then surgically transferred to synchronized recipient uteri. Only the trophectoderm cells are infected by the replication deficient virus, leaving the inner cell mass unaltered, and we often obtain ~70% pregnancy rates following transfer of a single blastocyst. In vivo RNAi coupled with steady-state study of blood flow and nutrient uptake, transfer and utilization can now provide new insight into the physiological consequences of modifying the translation of specific genes expressed within the ruminant placenta.