Role of prostaglandin I2 and prostaglandin E2 in the initiation of nonshivering thermogenesis during the simulation of birth in utero

1995 ◽  
Vol 7 (3) ◽  
pp. 399 ◽  
Author(s):  
KT Ball ◽  
M Takeuchi ◽  
Y Yoneyama ◽  
GG Power
Keyword(s):  
Fatty Acid ◽  
Umbilical Cord ◽  
Plasma Concentrations ◽  
Perinatal Period ◽  
In Utero ◽  
Nonshivering Thermogenesis ◽  
Prostaglandin I2 ◽  
Fetal Sheep ◽  
Near Term ◽  
High Concentrations

Because maximal nonshivering thermogenesis can commence only after occlusion of the umbilical cord, circulating stimulators and inhibitors were hypothesized to alter brown fat activity in the perinatal period. The roles of prostaglandin I2 (PGI2) and PGE2 in the initiation of nonshivering thermogenesis at birth were investigated. Indomethacin (45 mg bolus, 3 mg h-1 thereafter) was infused into 10 near-term fetal sheep to decrease prostanoid synthesis; 6 age-matched fetuses were infused with saline as controls. Sixteen hours later, birth was simulated in utero by sequentially cooling the fetus, ventilating its lungs with oxygen and occluding the umbilical cord. In the control fetuses, the plasma concentrations of PGI2 and PGE2 and free fatty acids, an index of nonshivering thermogenesis, were unaffected by cooling. Ventilation caused the concentration of PGI2 to increase 108% (P < 0.001) and that of PGE2 to decrease 26% (P < 0.05), while fatty acid concentrations increased 100% (P < 0.05). After cord occlusion, PGI2 concentrations remained elevated whereas PGE2 concentrations decreased a further 46% (P < 0.01), and fatty acid concentrations increased a further 100% (P < 0.05). In the indomethacin-treated fetuses, PGI2 and PGE2 concentrations decreased to 20% of the preinfusion values (P < 0.001) and did not change during the experiment. Cooling initiated a 300% increase in fatty acid concentrations (P < 0.05) and ventilation and cord occlusion induced no further significant changes. Thus, prostanoid concentrations follow changes in nonshivering thermogenic activity and support a regulatory role for PGI2 and PGE2 in the initiation of thermogenesis. Before birth, high concentrations of PGE2 favour suppression of thermogenesis, and after birth this inhibition is removed and there is stimulation by PGI2.

Suppressive action of endogenous adenosine on ovine fetal nonshivering thermogenesis

1996 ◽  
Vol 81 (6) ◽  
pp. 2393-2398 ◽  
Author(s):  
Karen T. Ball ◽  
Tania R. Gunn ◽  
Peter D. Gluckman ◽  
Gordon G. Power
Keyword(s):  
Umbilical Cord ◽  
In Utero ◽  
Quiescent State ◽  
Nonshivering Thermogenesis ◽  
Fetal Sheep ◽  
Adenosine Receptor Antagonist ◽  
Endogenous Adenosine ◽  
Brown Adipose ◽  
Ovine Fetal ◽  
Suppressive Action

Ball, Karen T., Tania R. Gunn, Peter D. Gluckman, and Gordon G. Power. Suppressive action of endogenous adenosine on ovine fetal nonshivering thermogenesis. J. Appl. Physiol. 81(6): 2393–2398, 1996.—Nonshivering thermogenesis is not initiated when the fetal sheep is cooled in utero but appears to require the removal of an inhibitor of placental origin at birth. To test whether adenosine is such an inhibitor, we examined the effect of the adenosine antagonist theophylline on the initiation of nonshivering thermogenesis during sequential cooling, ventilation, and umbilical cord occlusion in utero. Theophylline (18 mg/kg bolus and 0.6 mg ⋅ kg−1 ⋅ min−1thereafter) was infused for 90 min before and 90 min after cord occlusion. Theophylline enhanced the nonshivering thermogenic free fatty acid (FFA) and glycerol responses before cord occlusion, raising FFA concentrations 99% to 415 ± 60 μeq/l ( P < 0.01) and glycerol levels 87% to 526 ± 135 μmol/l ( P < 0.05). These FFA ( P < 0.001) and glycerol ( P < 0.05) concentrations were significantly greater than the corresponding period during the birth-simulation control. Umbilical cord occlusion did not alter FFA levels but induced a 41% rise in glycerol concentrations to 774 ± 203 μmol/l ( P < 0.05). The increases in nonshivering thermogenic indexes after the administration of the adenosine-receptor antagonist suggest that the quiescent state of ovine fetal brown adipose tissue may result, in part, from the tonic inhibitory actions of adenosine and that a decrease in adenosine concentrations enhances nonshivering thermogenesis. However, the further rise after umbilical cord occlusion suggests that at least one other inhibitor of placental origin inhibits nonshivering thermogenesis before birth.

scholarly journals Pancreas deficiency modifies bone development in the ovine fetus near term

2021 ◽  
Author(s):  
Stuart A Lanham ◽  
Dominique Blache ◽  
Richard Oc Oreffo ◽  
Abigail L Fowden ◽  
Alison J Forhead
Keyword(s):  
Mechanical Strength ◽  
Volume Fraction ◽  
Bone Structure ◽  
Plasma Concentrations ◽  
In Utero ◽  
Micro Computed Tomography ◽  
Bone Volume Fraction ◽  
Fetal Sheep ◽  
Trabecular Thickness ◽  
Near Term

Hormones have an important role in the regulation of fetal growth and development, especially in response to nutrient availability in utero. Using micro-computed tomography and an electromagnetic 3-point bend test, this study examined the effect of pancreas removal at 0.8 fraction of gestation on the developing bone structure and mechanical strength in fetal sheep. When fetuses were studied at 10 and 25 days after surgery, pancreatectomy caused hypoinsulinaemia, hyperglycaemia and growth retardation which was associated with low plasma concentrations of leptin and a marker of osteoclast activity and collagen degradation. In pancreatectomised fetuses compared to control fetuses, limb lengths were shorter and trabecular bone in the metatarsi showed greater bone volume fraction, trabecular thickness, degree of anisotropy and porosity, and lower fractional bone surface area and trabecular spacing. Mechanical strength testing showed that pancreas deficiency was associated with increased stiffness and a greater maximal weight load at fracture in a subset of fetuses studied near term. Overall, pancreas deficiency in utero slowed growth of the fetal skeleton and adapted the developing bone to generate a more compact and connected structure. Maintenance of bone strength in growth-retarded limbs is especially important in a precocial species in preparation for skeletal loading and locomotion at birth.

Effects of pancreatectomy on the growth and metabolite concentrations of the sheep fetus

1986 ◽  
Vol 110 (2) ◽  
pp. 225-231 ◽  
Author(s):  
A. L. Fowden ◽  
X. Z. Mao ◽  
R. S. Comline
Keyword(s):  
Body Weight ◽  
Plasma Insulin ◽  
Plasma Concentrations ◽  
Amino Nitrogen ◽  
In Utero ◽  
The Body ◽  
Fetal Sheep ◽  
Crown Rump Length ◽  
Metabolite Concentrations ◽  
Near Term

ABSTRACT The effects of fetal pancreatectomy on the growth and metabolism of the fetal sheep were investigated in chronically catheterized animals during the last third of gestation. Fetal pancreatectomy reduced body weight and crown–rump length at delivery near term (term 145 days). Body weight was affected more than body length so the ratio of weight to length was significantly less after pancreatectomy than in intact animals (P < 0·05). Pancreatectomized fetuses appeared to maintain a normal growth rate for 5–10 days after surgery but thereafter showed no further significant increase in body weight. When all the data from the intact and pancreatectomized fetuses were combined, there was a significant positive correlation between the plasma insulin concentration in utero and the body weight at delivery near term. The majority of organs studied were reduced in absolute weight after pancreatectomy but only the spleen and thymus were proportionally lighter when the weights were expressed as a percentage of body weight. Brain and placental weights were similar in intact and pancreatectomized fetuses. Over the range of values observed in utero, there were significant inverse correlations between the log plasma insulin level and the mean plasma concentrations of glucose, lactate, fructose and α-amino-nitrogen in individual intact and pancreatectomized fetuses. Insulin infusion into pancreatectomized fetuses restored the metabolite concentrations to their normal values within 48 h of infusion. The results demonstrate that insulin has a vital role in regulating fetal growth and metabolism in utero. J. Endocr. (1986) 110, 225–231

Heat production of fetal sheep brain in utero

1977 ◽  
Vol 43 (4) ◽  
pp. 747-749 ◽  
Author(s):  
R. M. Abrams ◽  
J. F. Clapp ◽  
M. Notelovitz ◽  
T. Tyler ◽  
S. Cassin
Keyword(s):  
Specific Heat ◽  
Heat Production ◽  
Brain Temperature ◽  
Main Pulmonary Artery ◽  
Fetal Brain ◽  
In Utero ◽  
Total Occlusion ◽  
Fetal Sheep ◽  
Sheep Brain ◽  
Near Term

Thermojunctions were implanted in the brains of 10 near term fetal sheep in utero under halothane anesthesia. Brief total occlusion of fetal brachiocephalic artery was followed immediately by an increase in brain temperature (mean +/- SE) of 0.130 +/- 0.014 degrees C-min-1. Occlusion of main pulmonary artery and ascending aorta, simultaneously, led to a brain temperature increase of 0.144 +/- 0.018 degrees C-min-1. Specific heat of three fetal brains was determined to be 0.898 +/- 0.014 cal-g-1. degrees C-1 or 3.76 +/- 0.059 J-g-1. Rate of fetal brain heat production, computed as the product of the higher rate of temperature change and brain specific heat, was 0.129 +/- 0.014 cal-g-1-min-1 or 9.00 +/- 0.98 mW-g-1.

scholarly journals Adrenal glands are essential for activation of glucogenesis during undernutrition in fetal sheep near term

2011 ◽  
Vol 300 (1) ◽  
pp. E94-E102 ◽  
Author(s):  
A. L. Fowden ◽  
A. J. Forhead
Keyword(s):  
Adrenal Glands ◽  
Metabolic Response ◽  
Glucose Production ◽  
Oxygen Metabolism ◽  
In Utero ◽  
Endogenous Glucose Production ◽  
Hepatic Glycogen ◽  
Fetal Sheep ◽  
Glucose Levels ◽  
Near Term

In adults, the adrenal glands are essential for the metabolic response to stress, but little is known about their role in fetal metabolism. This study examined the effects of adrenalectomizing fetal sheep on glucose and oxygen metabolism in utero in fed conditions and after maternal fasting for 48 h near term. Fetal adrenalectomy (AX) had little effect on the rates of glucose and oxygen metabolism by the fetus or uteroplacental tissues in fed conditions. Endogenous glucose production was negligible in both AX and intact, sham-operated fetuses in fed conditions. Maternal fasting reduced fetal glucose levels and umbilical glucose uptake in both groups of fetuses to a similar extent but activated glucose production only in the intact fetuses. The lack of fasting-induced glucogenesis in AX fetuses was accompanied by falls in fetal glucose ultilization and oxygen consumption not seen in intact controls. The circulating concentrations of cortisol and total catecholamines, and the hepatic glycogen content and activities of key gluconeogenic enzymes, were also less in AX than intact fetuses in fasted animals. Insulin concentrations were also lower in AX than intact fetuses in both nutritional states. Maternal glucose utilization and its distribution between the fetal, uteroplacental, and nonuterine maternal tissues were unaffected by fetal AX in both nutritional states. Ovine fetal adrenal glands, therefore, have little effect on basal rates of fetal glucose and oxygen metabolism but are essential for activating fetal glucogenesis in response to maternal fasting. They may also be involved in regulating insulin sensitivity in utero.

Relationship between the fall in growth hormone secretion at birth and the onset of nonshivering thermogenesis is independent of beta adrenergic stimulation

1995 ◽  
Vol 7 (5) ◽  
pp. 1237 ◽  
Author(s):  
KT Ball ◽  
TR Gunn ◽  
PD Gluckman
Keyword(s):  
Growth Hormone ◽  
Umbilical Cord ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Nonshivering Thermogenesis ◽  
Adrenergic Stimulation ◽  
Fetal Sheep ◽  
Beta Adrenergic ◽  
Rapid Fall ◽  
Plasma Ffa

At the time of birth, many rapid metabolic changes occur including the initiation of nonshivering thermogenesis and a rapid fall in growth hormone concentrations. To evaluate the interaction between these events 5 fetal sheep were studied at 135-144 days' gestation. The fetuses were first cooled 2.22 +/- 0.19 degrees C by circulating cold water through a coil placed around the fetal thorax and then ventilated with oxygen through an exteriorized tracheostomy tube to raise fetal arterial PO2 above 67.5 +/- 14.1 Torr. An hour later the beta adrenergic agonist isoproterenol was infused intravenously for 90 min. The fetuses were then separated from the placenta by occluding the umbilical cord. After 60 min the cooling and then the isoproterenol infusion were stopped and the responses monitored. Basal plasma free fatty acid (FFA 35 +/- 5 microEq L-1) and growth hormone (GH 141 +/- 12 ng mL-1) concentrations were not significantly altered by cooling alone, but oxygenation modestly increased plasma FFA to 237 +/- 55 microEq L-1 (P < 0.01) while GH concentrations fell to 58 +/- 27 ng mL-1 (P < 0.05). Isoproterenol administration did not significantly affect either FFA or GH concentrations. Occlusion of the umbilical cord caused a rapid nearly threefold increase in plasma FFA concentrations to 903 +/- 71 microEq L-1 (P < 0.01) and a fall in the same proportions in GH concentrations to 16 +/- 2 ng mL-1 (P < 0.005). Maximal fetal oxygen consumption was 24.2 +/- 4.4 mL kg-1 min-1. Cessation of cooling induced a significant fall in plasma FFA to 480 +/- 58 microEq L-1 (P < 0.01) and rise in GH concentrations to 46 +/- 5 ng mL-1 (P < 0.01). Following the withdrawal of isoproterenol, the fall in plasma FFA and rise in GH concentrations continued while the fetal oxygen uptake fell to 6.4 +/- 1.7 mliter kg-1 mL-1 (P < 0.01). During the study the variation in plasma GH was inversely correlated with changes in FFA concentrations (R = 0.77, P < 0.001). This study confirms that the major factors initiating nonshivering thermogenesis at birth are: sympathetic stimulation from cutaneous cooling, which was not significantly enhanced by isoproterenol; adequate oxygenation; and removal of placental inhibitor(s). The findings are in agreement with a causal relationship between the initiation of nonshivering thermogenesis and consequent rise in FFA concentrations and the rapid fall in circulating GH concentrations after birth in the lamb, independent of beta adrenergic stimulation.

ST waveform changes during repeated umbilical cord occlusions in near-term fetal sheep

2001 ◽  
Vol 184 (4) ◽  
pp. 743-751 ◽  
Author(s):  
Jenny A. Westgate ◽  
Laura Bennet ◽  
Christine Brabyn ◽  
Christopher E. Williams ◽  
Alistair J. Gunn
Keyword(s):  
Umbilical Cord ◽  
Fetal Sheep ◽  
Near Term

Generation of Periventricular Leukomalacia by Repeated Umbilical Cord Occlusion in Near-Term Fetal Sheep and Its Possible Pathogenetical Mechanisms

Neonatology ◽  
2001 ◽  
Vol 79 (1) ◽  
pp. 39-45 ◽  
Author(s):  
G. Marumo ◽  
S. Kozuma ◽  
J. Ohyu ◽  
Y. Hamai ◽  
Y. Machida ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Periventricular Leukomalacia ◽  
Fetal Sheep ◽  
Near Term

Glutamate Release from the Ovine Fetal Brain during Maternal Hemorrhage 

1995 ◽  
Vol 82 (2) ◽  
pp. 521-530 ◽  
Author(s):  
Donald H. Penning ◽  
David H. Chestnut ◽  
Franklin Dexter ◽  
James Hrdy ◽  
Dan Poduska ◽  
...  
Keyword(s):  
Parietal Cortex ◽  
Glutamate Release ◽  
Recovery Period ◽  
Fetal Brain ◽  
In Utero ◽  
Extracellular Glutamate ◽  
Microdialysis Probe ◽  
Fetal Sheep ◽  
Near Term ◽  
Ovine Fetal

Background Glutamate has been implicated in the pathophysiology of neuronal injury associated with cerebral hypoxia-ischemia. A model using chronic in utero microdialysis was developed to sample the extracellular space of the fetal brain. Using this model, we tested the hypothesis that glutamate efflux from the parasagittal parietal cortex of near-term fetuses would increase during maternal hemorrhage. Methods Twelve near-term fetal sheep were instrumented with vascular catheters, and a microdialysis probe(s) was implanted into the parasagittal parietal cortex. After a 3-day recovery period, the animals were subjected to maternal hemorrhage until either the fetal pH was &lt; 7.00 or the fetus died. The extracellular glutamate concentration in the collected dialysate was determined by high pressure liquid chromatography (HPLC). Results Maternal hemorrhage resulted in an 80-90% decrease in uterine blood flow, a decrease fetal po2, and a mixed metabolic and respiratory fetal acidosis. There were two groups of fetuses, survivors (n = 5) and nonsurvivors (n = 7). The nonsurvivor group showed a large increase (10-30-fold) in peak glutamate release (P = 0.0015). Survivors demonstrated a small (threefold) increase that was not statistically significant (P = 0.065), unless one animal with very low probe recovery was excluded (P = 0.0048). Conclusions Extracellular glutamate release from the fetal brain can occur during maternal hemorrhage with fetal acidemia. The pathophysiologic role (if any) of glutamate release in the survivors remains to be elucidated. Our results are consistent with the hypothesis that in utero release of glutamate occurs during periods of fetal asphyxia. This experimental preparation of chronic fetal brain microdialysis can be used to monitor the brain extracellular concentration of any dialyzable substance in response to stress, including maternal hemorrhage.

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