Fetal insulin-like growth factor (IGF)-I and IGF-II are regulated differently by glucose or insulin in the sheep fetus

1996 ◽  
Vol 8 (1) ◽  
pp. 167 ◽  
Author(s):  
MH Oliver ◽  
JE Harding ◽  
BH Breier ◽  
PD Gluckman

We investigated the effect of restoration of normoglycaemia or normoinsulinaemia in fetuses of starved ewes on plasma IGF-I and IGF-II concentrations. Paired maternal and fetal blood samples were taken during an initial 2-day control period, after 48 h of maternal starvation, during 24 h fetal infusion of glucose (n = 6) or insulin (n = 4) while maintaining maternal starvation and after 48 h maternal refeeding. After 48 h starvation maternal and fetal plasma IGF-I, insulin and blood glucose fell (maternal IGF-I 38.9 +/- 3.6 to 16.4 +/- 1.8 nM and fetal IGF-I 13.2 +/- 0.8 to 7.1 +/- 0.7 nM, both P < 0.05). Fetal plasma IGF-II also fell (147.8 +/- 9.1 to 112.2 +/- 3.8 nM, P < 0.05), but maternal plasma IGF-II rose (71.8 +/- 6.3 to 88.8 +/- 9.2 nM, P = 0.10). Fetal glucose replacement raised fetal plasma IGF-I (11.4 +/- 1.2 nM), IGF-II (149.7 +/- 6.5 nM), insulin and blood glucose to near control values (all P < 0.05). Fetal insulin replacement raised fetal plasma IGF-I (9.0 +/- 0.6 nM) and insulin (all P < 0.05) while IGF-II (105.2 +/- 8.4 nM) and blood glucose remained depressed. Neither fetal infusion had any significant effect on maternal plasma IGF-I (13.1 +/- 1.6 nM), IGF-II (77.5 +/- 8.7 nM), insulin or blood glucose. After 48 h maternal refeeding fetal IGF-I (12.4 +/- 0.4 nM), fetal IGF-II (158.4 +/- 8.9 nM), maternal IGF-II (67.1 +/- 3.0 nM), maternal and fetal insulin and glucose had returned to near control values in both groups. Maternal IGF-I remained below control values (24.7 +/- 2.5 nM, P < 0.05). The data suggest that fetal IGF-I and IGF-II are independently regulated in the fetal circulation. While glucose plays an important role in the regulation of both IGF-I and IGF-II, the influence of glucose on fetal IGF-I is likely to be mediated by insulin, whereas for IGF-II the effect of glucose is insulin-independent.

2003 ◽  
Vol 177 (1) ◽  
pp. 83-92 ◽  
Author(s):  
MK Bauer ◽  
BB Breier ◽  
FH Bloomfield ◽  
EC Jensen ◽  
PD Gluckman ◽  
...  

Intra-uterine growth restriction (IUGR) is a major cause of perinatal mortality and morbidity. Postnatally, growth hormone (GH) increases growth, increases circulating insulin-like growth factor (IGF)-I levels, and alters metabolism. Our aim was to determine if GH infusion to IUGR fetal sheep would alter fetal growth and metabolism, and thus provide a potential intra-uterine treatment for the IUGR fetus. We studied three groups of fetuses: control, IUGR+ vehicle and IUGR+GH (n=5 all groups). IUGR was induced by repeated embolisation of the placental vascular bed between 110 and 116 days of gestation (term=145 days). GH (3.5 mg/kg/day) or vehicle was infused in a pulsatile manner from 117 to 127 days of gestation. Embolisation reduced fetal growth rate by 25% (P<0.01) and reduced the weight of the fetal liver (20%), kidney (23%) and thymus (31%; all P<0.05). GH treatment further reduced the weight of the fetal kidneys (32%) and small intestine (35%; both P<0.04), but restored the relative weight of the fetal thymus and liver (P<0.05). Embolisation decreased fetal plasma IGF-I concentrations (48%, P<0.001) and increased IGF binding protein 1 (IGFBP-1) concentrations (737%, P<0.002). GH treatment restored fetal plasma IGF-I concentrations to control levels, while levels in IUGR+vehicle fetuses stayed low (P<0.05 vs control). IGFBP-1 and IGFBP-2 concentrations were about sevenfold lower in amniotic fluid than in fetal plasma, but amniotic and plasma concentrations were closely correlated (r=0.75, P<0.0001 and r=0.55 P<0.0001 respectively). Embolisation transiently decreased fetal blood oxygen content (40%, P<0.002), and increased blood lactate concentrations (213%, P<0.04). Both returned to pre-embolisation levels after embolisation stopped, but blood glucose concentrations declined steadily in IUGR+vehicle fetuses. GH treatment maintained fetal blood glucose concentrations at control levels. Our study shows that GH infusion to the IUGR fetal sheep restores fetal IGF-I levels but does not improve fetal growth, and further reduces the fetal kidney and intestine weights. Thus, fetal GH therapy does not seem a promising treatment stratagem for the IUGR fetus.


1995 ◽  
Vol 144 (2) ◽  
pp. 333-338 ◽  
Author(s):  
M H Oliver ◽  
J E Harding ◽  
B H Breier ◽  
P C Evans ◽  
B W Gallaher ◽  
...  

Abstract It has been suggested, but not shown, that in the fetus placental lactogen (PL) may affect the regulation of the IGFs and fetal metabolism. To examine the effects of PL on the circulating concentrations of the IGFs, IGF-binding proteins (IGFBPs), glucose, free fatty acids (FFAs) and amino nitrogen (AN), we infused late gestation sheep fetuses with recombinant ovine PL (roPL). Five chronically-catheterised sheep fetuses were infused intravenously with three 24 h infusions of saline, roPL (100 μg bolus then 500 μg over 24 h) and then saline again. Fetal roPL infusion increased plasma oPL from 0·4 ± 0·1 to 3·3 ± 0·5 nm (mean ± s.e.m.; P<0·05; factorial analysis of variance and Scheffé's test). Fetal plasma IGF-I, IGF-II, insulin, FFAs and blood glucose were unaffected by the roPL infusion. Fetal plasma IGFBP-3, as measured by Western ligand blotting, decreased by 30% during fetal roPL infusion while other fetal plasma IGFBPs were unaffected. Fetal roPL infusion decreased fetal blood AN from 7·3 ± 0·5 to 6·6 ± 0·2 mm (P<0·05). Maternal plasma IGF-I, IGF-II, IGFBPs, insulin, FFAs, blood glucose and AN were unaffected by the fetal roPL infusion. Saline infusion had no effect on any parameter. The data suggest that PL is not a significant determinant of plasma IGFs in the late gestation sheep fetus although there may be an indirect effect via alterations in levels of IGFBP-3. The effect of fetal roPL infusion on fetal blood AN concentrations may suggest some role for PL in the regulation of fetal amino acid metabolism. Journal of Endocrinology (1995) 144, 333–338


1993 ◽  
Vol 264 (1) ◽  
pp. R197-R203 ◽  
Author(s):  
C. L. Agnew ◽  
M. G. Ross ◽  
Y. Fujino ◽  
M. G. Ervin ◽  
L. Day ◽  
...  

Dehydration induces marked alterations in maternal-fetal fluid homeostasis and accompanying fetal endocrine responses. We sought to determine if the increase in fetal plasma arginine vasopressin (AVP) levels during maternal dehydration is mediated by fetal plasma hypovolemia in addition to hyperosmolality and to examine maternal and fetal plasma atrial natriuretic factor (ANF) responses to maternal dehydration and oral rehydration. Seven pregnant ewes (127 +/- 1 day) were water deprived for 72-96 h, and five of these were orally rehydrated. Dehydration induced significant increases in maternal plasma osmolality (pOSM) (300 +/- 2 to 325 +/- 8 mosmol/kg) and AVP (3.0 +/- 0.4 to 18.9 +/- 4.0 pg/ml), and decreases in plasma ANF levels (28.1 +/- 3.1 to 19.7 +/- 3.1 pg/ml). Fetal pOSM (293 +/- 3 to 314 +/- 4 mosmol/kg), AVP (2.5 +/- 0.6 to 8.1 +/- 4.8 pg/ml), and urinary fractional sodium excretion increased significantly, whereas plasma ANF and fetal blood volume did not change. After maternal water access maternal plasma AVP decreased rapidly in comparison to the gradual decrease in maternal pOSM. Fetal plasma AVP levels did not change significantly and fetal pOSM decreased more slowly than maternal pOSM. Fetal plasma ANF increased in association with increased urine flow and glomerular filtration rate after maternal rehydration. These data indicate marked differences in fetal and maternal plasma ANF and AVP responses with dehydration-induced increases in fetal plasma AVP being secondary to plasma hyperosmolality, rather than hypovolemia. Rapid suppression of maternal plasma AVP may contribute to the slower equilibration of fetal pOSM during oral, as compared with intravenous, maternal rehydration.


PEDIATRICS ◽  
1960 ◽  
Vol 25 (1) ◽  
pp. 2-10
Author(s):  
Frederick Battaglia ◽  
Harry Prystowsky ◽  
Clayton Smisson ◽  
Andre Hellegers ◽  
Paul Bruns

The normal relationship between fetal and maternal plasma of total osmotic pressures and concentrations of sodium and potassium were determined in women with uncomplicated pregnancies at full term. The total osmotic pressure of fetal plasma was found to be 3.6 mOsm/kg of water higher than the maternal, probably not representing a physiologically significant difference. No significant difference in sodium concentrations of plasma was found. The potassium concentration in the fetal plasma was 0.7 meq/l higher than in the maternal plasma. The administration of 5% glucose or 20% mannitol intravenously to pregnant women prior to delivery was shown to have a prompt effect upon the total osmotic pressure and concentration of sodium and total protein of fetal plasma.


1995 ◽  
Vol 268 (2) ◽  
pp. R358-R365 ◽  
Author(s):  
M. J. Nijland ◽  
M. G. Ross ◽  
L. K. Kullama ◽  
K. Bradley ◽  
M. G. Ervin

Fetal urine flow is influenced by fetal intravascular volume, glomerular filtration rate, tubular reabsorption, and fluid regulatory hormones. As maternal-to-fetal fluid transfer is dependent on hydrostatic and osmotic gradients, we postulated that a chronic decrease in maternal plasma osmolality would promote transplacental fluid transfer and increase fetal urine flow. Six pregnant ewes and singleton fetuses (131 +/- 2 days; term = 150 days) received bladder and hindlimb arterial and venous catheters. After 5 days, plasma and urine composition, urine flow rate (Uvol), and plasma arginine vasopressin (AVP) levels were measured during a 2-h control period. At 2 h, tap water (2 liter, 38 degrees C) was administered to the ewe. At 3 h, ewes received a 20-micrograms bolus of 1-desamino-[D-Arg8]vasopressin (DDAVP), followed by continuous infusion (4 micrograms/h). In response to water loading, maternal urine osmolality decreased (761 +/- 158 to 339 +/- 13 mosmol/kgH2O), and Uvol increased. After DDAVP, maternal urine osmolality increased (1,270 +/- 89 mosmol/kgH2O), and Uvol, hematocrit, plasma osmolality (304 +/- 1 to 284 +/- 4 mosmol/kgH2O), and protein concentration decreased. Five hours after maternal DDAVP infusion, fetal plasma osmolality decreased (300 +/- 1 to 281 +/- 3 mosmol/kgH2O), and Uvol increased (0.4 +/- 0.1 to 1.3 +/- 0.2 ml/min) and remained elevated at 24 h. There was no change in fetal plasma DDAVP (immunoreactive AVP) levels or fetal urine osmolality. Controlled changes in maternal plasma osmolality may prove useful in modulating fetal urine flow and, ultimately, amniotic fluid volume.


Endocrinology ◽  
2007 ◽  
Vol 148 (11) ◽  
pp. 5424-5432 ◽  
Author(s):  
J. T. Ross ◽  
I. C. McMillen ◽  
F. Lok ◽  
A. G. Thiel ◽  
J. A. Owens ◽  
...  

We investigated the effects of an intrafetal infusion of IGF-I on adrenal growth and expression of the adrenal steroidogenic and catecholamine-synthetic enzyme mRNAs in the sheep fetus during late gestation. Fetal sheep were infused for 10 d with either IGF-I (26 μg/kg·h; n = 14) or saline (n = 10) between 120 and 130 d gestation, and adrenal glands were collected for morphological analysis and determination of the mRNA expression of steroidogenic and catecholamine-synthetic enzymes. Fetal body weight was not altered by IGF-I infusion; however, adrenal weight was significantly increased by 145% after IGF-I infusion. The density of cell nuclei within the fetal adrenal cortex (the zona glomerulosa and zona fasciculata), and within the adrenaline synthesizing zone of the adrenal medulla, was significantly less in the IGF-I-infused fetuses compared with the saline-infused group. Thus, based on cell-density measurements, there was a significant increase in cell size in the zona glomerulosa and zona fasciculata of the adrenal cortex and in the adrenaline-synthesizing zone of the adrenal medulla. There was no effect of IGF-I infusion on the adrenal mRNA expression of the steroidogenic or catecholamine-synthetic enzymes or on fetal plasma cortisol concentrations. In summary, infusion of IGF-I in late gestation resulted in a marked hypertrophy of the steroidogenic and adrenaline-containing cells of the fetal adrenal in the absence of changes in the mRNA levels of adrenal steroidogenic or catecholamine-synthetic enzymes or in fetal plasma cortisol concentrations. Thus, IGF-I infusion results in a dissociation of adrenal growth and function during late gestation.


1968 ◽  
Vol 46 (1) ◽  
pp. 43-45 ◽  
Author(s):  
Sun Shik Shim ◽  
D. Harold Copp ◽  
Frank P. Patterson

Ten dogs were anesthetized with pentobarbital, and after a control period of at least 1 h, during which three blood samples were taken, adrenaline (2–4 μg/kg per min) was infused intravenously for 1 h. Blood samples were taken at 15- or 30-min intervals during the infusion and for 2 h thereafter. These were analyzed for calcium, inorganic phosphate, and glucose. The plasma calcium level did not change significantly during or following the infusion; however, the plasma glucose rose and the plasma phosphate fell during adrenaline administration. The glucose level returned to normal within 2 h of termination of the infusion; in some dogs the plasma phosphate also returned to the control level, whereas in others it remained depressed at this time.


1999 ◽  
Vol 87 (4) ◽  
pp. 1440-1447 ◽  
Author(s):  
Todd J. Roberts ◽  
Mark J. M. Nijland ◽  
Leslee Williams ◽  
Michael G. Ross

Maternal hyponatremia induces fetal hyponatremia and increased fetal urine flow. We sought to examine the relative contributions of the placental Na+gradient vs. the absolute decrease in fetal plasma Na+ in the fetal diuretic response to hyponatremia. Seven ewes with singleton fetuses (130 ± 2 days) were prepared. Ewes received intravenous 1-desamino-8-d-arginine vasopressin (20 μg) and warm tap water (2 liters). Maternal plasma Na+ was decreased to achieve two levels of maternal hyponatremia. Maternal and fetal blood volume were measured with radiolabeled red blood cells. In response to the first decrease in maternal plasma Na+, fetal plasma Na+ did not change initially. Subsequently, fetal plasma Na+ decreased, normalizing the gradient. The second decrease in maternal plasma Na+ similarly induced a reduced and normalized placental gradient at lower fetal plasma Na+ values. Fetal urine flow increased in direct proportion to the degree of fetal hyponatremia (13, 38, 63, 100%, respectively). Maternal, although not fetal, blood volume significantly increased in response to hyponatremia. These results suggest that chronic fetal hyponatremia will result in a persistent diuresis, despite placental equilibration.


2020 ◽  
Vol 70 (4) ◽  
pp. 355-358
Author(s):  
Gabrielle C Musk ◽  
Haruo Usuda ◽  
Helen Kershaw ◽  
Matthew W Kemp ◽  
Claire R Sharp

To determine the incidence of ex vivo incompatibility between ovine maternal RBCs and fetal plasma, we performed cross-matching of blood samples from ewes and from lambs delivered by cesarean section. Twenty-one date-mated singleton pregnant Merino ewes were anesthetized for cesarean delivery of the fetus. At the time of delivery, paired maternal and fetal blood samples were collected and subsequently separated for storage as packed red blood cells and fresh frozen plasma. Gel column major cross matching was performed within 2 wk. All fetus-dam crossmatches were major crossmatches, combining fetal (recipient) plasma with dam (donor) RBCs. 172 individual dam-dam cross matches were performed. Two of these tests were incompatible (1.2%). In addition, 19 fetal blood samples collected immediately after cesarean delivery were crossmatched with 21 maternal samples to generate 174 maternal-fetal individual cross matches. No maternal-fetal incompatibility reactions were observed. The results of this study demonstrate that all maternal donors and fetal recipients were compatible. In addition, the incidence of an incompatible crossmatch between adult ewes was 1.2%. These data suggest that lambs may not be born with antibodies against other blood types, but rather may acquire such antibodies at some time during early life. In addition, these data suggest the risk of incompatibility reactions between ewes of a similar breed and from a single farm of origin is very low.


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