scholarly journals 273.Insulin-like growth factor treatment of pregnant guinea pigs during early pregnancy promotes fetal growth

2004 ◽  
Vol 16 (9) ◽  
pp. 273
Author(s):  
A. N. Sferruzzi-Perri ◽  
J. A. Owens ◽  
J. S. Robinson ◽  
C. T. Roberts
Keyword(s):  
Growth Factor ◽  
Fetal Growth ◽  
Early Pregnancy ◽  
Guinea Pigs ◽  
Placental Weight ◽  
Fetal Weight ◽  
Abdominal Circumference ◽  
Insulin Like Growth Factor ◽  
Crown Rump Length ◽  
Igf I

Insulin-like growth factor (IGF)-II is an important regulator of growth in many tissues and is abundantly expressed in the placenta during pregnancy. Gene ablation studies performed in mice have shown that IGF-II deficiency results in both impaired fetal and placental growth, whereas deficiency in IGF-I reduces fetal growth only. Conversely, maternal IGF supplementation in early pregnancy in the guinea pig increases placental and fetal size by mid pregnancy. This study aimed to determine whether these anabolic effects persist into late pregnancy after cessation of treatment. On Day 20 of pregnancy, mothers were anaesthetised and a mini osmotic pump was implanted subcutaneously, to deliver 1mg/kg/day IGF-I (n = 7), IGF-II (n = 9) or vehicle (n = 7) for 17 days. Guinea pigs were killed on Day 62 of pregnancy (term ~67 days). Fetal and placental weights, and maternal and fetal body composition, were measured. Total litter size was unaffected by IGF treatment; however, IGF-II increased the number of viable fetuses by 26% (P = 0.01). After adjusting for the number of viable pups per litter, maternal IGF treatment increased fetal growth by increasing abdominal circumference, crown-rump length and fetal weight (fetal weight: IGF-I 79+/–2.5 g; IGF-II 78+/–2.6 g; vs vehicle 68+/–2.5 g, P = 0.02). IGF treatment did not alter absolute or relative fetal organ weights. IGF-I reduced placental weight by 9% and IGF-II increased it by 9%, but not significantly. IGF-I increased the fetal weight�:�placental weight ratio (19+/–0.9 vs 15+/–0.9, respectively P = 0.043). IGF treatment did not affect maternal weight gain during pregnancy nor net carcass weight; however, IGF-I reduced maternal lung and adipose tissue weights. In conclusion, maternal IGF-II treatment during early pregnancy improved fetal growth into late gestation, possibly by modulating placental efficiency. As poor placental development is implicated in fetal growth restriction, increasing maternal IGF abundance in early to mid pregnancy may be a potential therapeutic approach to placental insufficiency.

Maternal nutrient restriction during early to mid gestation alters the relationship between insulin-like growth factor I and bodyweight at term in fetal sheep

2000 ◽  
Vol 12 (8) ◽  
pp. 345 ◽  
Author(s):  
Lindsay Heasman ◽  
John Brameld ◽  
Alison Mostyn ◽  
Helen Budge ◽  
Janet Dawson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Metabolizable Energy ◽  
Fetal Weight ◽  
Nutrient Restriction ◽  
Insulin Like Growth Factor ◽  
Fetal Sheep ◽  
Crown Rump Length ◽  
Hepatic Expression ◽  
Igf I ◽  
The Relationship

The present study was designed to determine whether altered placental size, as a consequence of maternal nutrient restriction in sheep between 28 and 77 days gestation, is associated with a modified relationship between fetal weight or dimensions and plasma insulin-like growth factor (IGF) I concentration or abundance of hepatic IGF-I and IGF-II mRNA close to term. Singleton-bearing ewes consumed either 1.2 (controls, n = 19) or 0.5 (nutrient restricted, n = 28) their metabolizable energy (ME) requirements from 28 to 77 days gestation, after which all ewes were fed in order to fully meet their ME requirements for maintenance and pregnancy. Close to term (145 1 days) plasma IGF-I concentration in cord blood was similar between groups, but only significantly correlated with fetal bodyweight, thoracic circumference, crown–rump length and lean body mass in lambs born to control (r2 = 0.38, 0.76, 0.33, 0.42; P<0.001), and not to nutrient-restricted (r2 = 0.01, 0.11, 0.01, 0.02) ewes. There were no differences in fetal hepatic expression of IGF-I and IGF-II mRNA between groups close to term. In conclusion, maternal nutrient restriction in early to mid gestation followed by feeding to requirements up to term alters the relationship between fetal IGF-I, bodyweight and length. Increasing maternal nutrition in later gestation after a prolonged period of nutrient restriction may stimulate fetal nutrient supply such that fetal growth is enhanced without an increase in plasma IGF-I. As a result, there is a loss of the relationship between fetal weight and plasma IGF-I concentration observed in fetuses whose mothers are fed adequately throughout gestation.

ELEVATING MATERNAL INSULIN-LIKE GROWTH FACTOR-I IN MICE AND RATS ALTERS THE PATTERN OF FETAL GROWTH BY REMOVING MATERNAL CONSTRAINT

1992 ◽  
Vol 134 (1) ◽  
pp. R1-R3 ◽  
Author(s):  
P.D. Gluckman ◽  
P.C.H. Morel ◽  
G.R. Ambler ◽  
B.H. Breier ◽  
H.T. Blair ◽  
...  
Keyword(s):  
Body Weight ◽  
Growth Factor ◽  
Litter Size ◽  
Fetal Growth ◽  
Negative Relationship ◽  
Late Gestation ◽  
Fetal Weight ◽  
Insulin Like Growth Factor ◽  
Direct Role ◽  
Igf I

ABSTRACT Fetal growth is normally constrained by maternal factors. This constraint is demonstrated by the usual inverse linear relationship between litter size and mean fetal weight. Cross-breeding experiments between mice of lines selected for high or low plasma insulin-like growth factor (IGF-I) levels suggested that elevations in maternal IGF-I abolish (P <0.01) this constraining effect and reverse the usual positive relationship between fetal and placental size in late gestation. This was confirmed by treating mice and rats throughout pregnancy with IGF-I. In normal mice and in low IGF-I line mice treatment with IGF-I 10μg 8-hourly s.c. from day 1 to 19 of pregnancy) abolished maternal constraint whereas 0.9% (w/v) NaCl treatment did not. In Wistar rats osmotic pumps were implanted to deliver IGF-I (1μg/g body weight per day), bovine GH (bGH; 0.6μg/g body weight per day) or saline from day 1 to 19 of pregnancy. IGF-I therapy but not bGH or saline abolished (P < 0.01) maternal constraint and altered (P <0.01) the relationship between placental and fetal weight. When high or low IGF-I line mice embryos were transplanted into a normal line of mice, the expected negative relationship (P <0.05) between mean fetal weight and litter size was maintained. However the embryos of the high line were heavier (P <0.05) than those from the low line irrespective of fetal number, suggesting a direct role for IGF-I in the regulation of fetal growth. Thus both endogenous and exogenous elevations in maternal IGF-I indirectly promote fetal growth either by altering nutrient delivery to the placenta or by affecting placental function.

The concentration of insulin-like growth factor-I and insulin-like growth factor-binding protein-1 in human umbilical cord serum at delivery: relation to fetal weight

1991 ◽  
Vol 129 (3) ◽  
pp. 459-464 ◽  
Author(s):  
H. S. Wang ◽  
J. Lim ◽  
J. English ◽  
L. Irvine ◽  
T. Chard
Keyword(s):  
Growth Factor ◽  
Umbilical Cord ◽  
Fetal Growth ◽  
Gestational Age ◽  
Umbilical Artery ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Factor I ◽  
Igf I

ABSTRACT Serum levels of insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-1 (IGFBP-1) have been determined by radioimmunoassay in the maternal circulation (n = 91) and in the umbilical artery (n = 56) and vein (n = 90) of man. In both the umbilical artery and vein, the concentration of serum IGF-I showed an inverse correlation with birthweight (P < 0·005 and P < 0·001 respectively); the mean serum IGF-I levels in the small-for-gestational-age (SGA) group were significantly higher than those in average-for-gestational-age (AGA) neonates (P <0·01 and P < 0·001 respectively). However, maternal serum IGF-I showed no association with birthweight and there was no significant difference between the SGA and AGA groups. These observations imply that the production of IGF-I in the maternal and fetal compartments is independent and that there is unlikely to be transfer of IGF-I across the placenta. Serum IGFBP-1 levels in both maternal and umbilical cord blood (artery and vein) showed an inverse relation to birthweight (P <0·001, P<0·005 and P<0·001 respectively). Increased IGFBP-1 levels in the umbilical artery and vein were observed in the SGA group. These findings suggest that IGFBP-1 might inhibit the action of IGF-I in both the maternal and the fetal compartments and that the rise in IGFBP-1 could be a primary factor in retardation of fetal growth. Alternatively, circulating IGF-I and IGFBP-1 levels may only be a secondary reflection of local tissue events involved in fetal growth. Journal of Endocrinology (1991) 129, 459–464

Effects of glucocorticoid treatment given in early or late gestation on growth and development in sheep

2013 ◽  
Vol 4 (2) ◽  
pp. 146-156 ◽  
Author(s):  
S. Li ◽  
D. M. Sloboda ◽  
T. J. M. Moss ◽  
I. Nitsos ◽  
G. R. Polglase ◽  
...  
Keyword(s):  
Growth Factor ◽  
Early Pregnancy ◽  
Plasma Insulin ◽  
Fetal Brain ◽  
Late Gestation ◽  
Fetal Weight ◽  
Postnatal Life ◽  
Insulin Like Growth Factor ◽  
Organ Weights ◽  
Fetal Organ

Antenatal corticosteroids are used to augment fetal lung maturity in human pregnancy. Dexamethasone (DEX) is also used to treat congenital adrenal hyperplasia of the fetus in early pregnancy. We previously reported effects of synthetic corticosteroids given to sheep in early or late gestation on pregnancy length and fetal cortisol levels and glucocorticoids alter plasma insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) concentrations in late pregnancy and reduce fetal weight. The effects of administering DEX in early pregnancy on fetal organ weights and betamethasone (BET) given in late gestation on weights of fetal brain regions or organ development have not been reported. We hypothesized that BET or DEX administration at either stage of pregnancy would have deleterious effects on fetal development and associated hormones. In early pregnancy, DEX was administered as four injections at 12-hourly intervals over 48 h commencing at 40–42 days of gestation (dG). There was no consistent effect on fetal weight, or individual fetal organ weights, except in females at 7 months postnatal age. When BET was administered at 104, 111 and 118 dG, the previously reported reduction in total fetal weight was associated with significant reductions in weights of fetal brain, cerebellum, heart, kidney and liver. Fetal plasma insulin, leptin and triiodothyronine were also reduced at different times in fetal and postnatal life. We conclude that at the amounts given, the sheep fetus is sensitive to maternal administration of synthetic glucocorticoid in late gestation, with effects on growth and metabolic hormones that may persist into postnatal life.

scholarly journals Loss of the pregnancy-induced rise in cortisol concentrations in the ewe impairs the fetal insulin-like growth factor axis

2011 ◽  
Vol 23 (5) ◽  
pp. 665 ◽  
Author(s):  
Ellen C. Jensen ◽  
Laura Bennet ◽  
Charles Wood ◽  
Mark Vickers ◽  
Bernhard Breier ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fetal Growth ◽  
Fetal Liver ◽  
Plasma Concentrations ◽  
Late Gestation ◽  
Control Group ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Igf I ◽  
Low Cortisol

Maternal cortisol levels increase during pregnancy. Although this change is important for optimal fetal growth, the mechanisms of the changes in growth remain unclear. The hypothesis examined was that alterations in maternal plasma cortisol concentrations are associated with changes in the fetal insulin-like growth factor (IGF) axis. Pregnant ewes in late gestation (115 ± 0.4 days) were studied: six control animals, five ewes given 1 mg kg–1 day–1 cortisol (high cortisol) and five adrenalectomised ewes given 0.5–0.6 mg kg–1 day–1 cortisol (low cortisol). Blood samples were taken throughout the experiment and at necropsy (130 ± 0.2 days) and fetal liver was frozen for mRNA analysis. Fetal IGF-I and insulin plasma concentrations were lower and insulin-like growth factor-binding protein-1 (IGFBP-1) concentrations were higher in the low cortisol group compared with those in the control group (P < 0.05). Fetal liver IGF-II and IGFBP-3 mRNA were decreased in low cortisol animals compared with controls (P < 0.05). There were no significant changes in these parameters in the high cortisol group, and there were no changes in fetal liver IGF-I, growth hormone receptor, IGF-I receptor, IGF-II receptor, IGFBP-1 or IGFBP-2 mRNA levels between the groups. These data suggest that reduced fetal IGF availability contributes to reduced fetal growth when maternal cortisol secretion is impaired, but not during exposure to moderate increases in cortisol.

Insulin-like growth factor I promotes growth selectively in fetal sheep in late gestation

1996 ◽  
Vol 270 (5) ◽  
pp. R1148-R1155 ◽  
Author(s):  
F. Lok ◽  
J. A. Owens ◽  
L. Mundy ◽  
J. S. Robinson ◽  
P. C. Owens
Keyword(s):  
Growth Factor ◽  
Fetal Growth ◽  
Late Gestation ◽  
Skeletal Maturation ◽  
Long Bones ◽  
Insulin Like Growth Factor ◽  
Fetal Sheep ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Insulin-like growth factor I (IGF-I) is required for normal fetal growth and skeletal maturation in late gestation, because null mutations of the IGF-I gene in mice reduce fetal weight and retard ossification of bones. To determine if, conversely, increased abundance of IGF-I promotes fetal growth and skeletal maturation, fetal sheep were infused intravascularly with recombinant human IGF-I (n = 7) (26 +/- 3 micrograms. h-1.kg-1) from 120 to 130 days gestation and compared with controls (n = 15). IGF-I infusion increased plasma IGF-I concentrations by 140% (P = 0.002) and weights of fetal liver, lungs, heart, kidneys, spleen, pituitary, and adrenal glands by 16-50% (P < 0.05). Weights and/or lengths of the fetus, placenta, gastrointestinal tract, individual skeletal muscles, and long bones were unchanged by IGF-I. However, IGF-I increased the percentage of proximal epiphyses of long bones present (P < 0.05) and their cross-sectional areas by 15 to 38% (P < 0.05). These results show that IGF-I promotes growth of major fetal organs, endocrine glands, and skeletal maturation in vivo, consistent with IGF-I actively controlling and not merely facilitating fetal growth. The variable response of different tissues may partly reflect tissue specificity in growth requirements for additional factors.

scholarly journals Effect of maternal body condition on placental and fetal growth and the insulin-like growth factor axis in Dorset ewes

Reproduction ◽  
2003 ◽  
pp. 717-731 ◽  
Author(s):  
JC Osgerby ◽  
TS Gadd ◽  
DC Wathes
Keyword(s):  
Growth Factor ◽  
Body Condition ◽  
Fetal Growth ◽  
Body Condition Score ◽  
Insulin Like Growth Factor ◽  
Maternal Body ◽  
Crown Rump Length ◽  
Condition Score ◽  
Moderate Condition ◽  
Igfbp 3

This study investigated the effects of maternal body condition on fetal growth. Fetal and placental parameters from Dorset ewes of body condition score 2.0 (lean, n = 5), 3.5 (moderate, n = 7) and 5.0 (fat, n = 4) at mating were studied on day 65 of gestation. The fetal weight and fetal weight:crown-rump length ratio were greater in fat ewes than in ewes of moderate condition. The raised total and mean placentome weight in fat ewes compared with ewes of moderate condition may have contributed to their increased fetal growth. However, the fetal crown-rump length was not affected. With in situ hybridization, insulin-like growth factor II (IGF-II) mRNA and insulin-like growth factor binding protein 2 (IGFBP-2), -3 and -6 were all detected in the placentome capsule; IGF-II mRNA was also found in the mesoderm of the fetal villi and IGFBP-3 and IGFBP-6 were present in the caruncular stroma of the maternal villi. Ewes of moderate condition, which had the smallest placentae, had the greatest placental expression of IGF-II, IGFBP-2 and IGFBP-3. In the intercotyledonary endometrium, IGFBP-3, IGFBP-5 and uterine milk protein (UTMP) mRNA were all expressed in the glandular epithelium. IGFBP-3 and IGFBP-5 absorbance values were lowest in the lean ewes, whereas UTMP values were highest. Maternal insulin concentrations were greater in fat ewes, whereas plasma glucose and IGF-I concentrations in the fetal compartment were lowest in fat ewes. Therefore, in obese ewes, fetal and placental growth is increased in mid-gestation in association with higher maternal insulin concentrations and lower expression of IGFBPs in the maternal placentomes. Placental and fetal development in lean ewes may be promoted by reduced IGFBP expression in the placentomes and enhanced UTMP production by the endometrial glands. The ewes of moderate condition had the smallest fetuses and placentae coupled with the highest placental expression of IGF-II and IGFBPs.

Effects of passive immunization of growing guinea-pigs with an insulin-like growth factor-I monoclonal antibody

1990 ◽  
Vol 124 (3) ◽  
pp. 403-415 ◽  
Author(s):  
D. E. Kerr ◽  
B. Laarveld ◽  
J. G. Manns
Keyword(s):  
Monoclonal Antibody ◽  
Growth Factor ◽  
Guinea Pigs ◽  
Treated Group ◽  
Insulin Like Growth Factor ◽  
Local Production ◽  
Factor I ◽  
Igf I ◽  
Animal Growth ◽  
Growth Factor I

ABSTRACT The physiological importance of circulating as opposed to locally produced insulin-like growth factor-I (IGF-I) has not been determined. By using a passive immunoneutralization technique, our objectives were to evaluate the role of circulating IGF-I in the regulation of animal growth and pituitary GH content. A monoclonal antibody (MAb) to IGF-I, generated in our laboratory, has an affinity (Ka) of 0·13 litres/pmol for recombinant human IGF-I (rhIGF-I). Cross-reactivities of recombinant des-tripeptide IGF-I and recombinant bovine IGF-II were approximately 40 and 8% respectively. This MAb inhibited binding of purified hIGF-I to human placental membranes. In a radioimmunoassay based on displacement of 125I-labelled rhIGF-I from the MAb, displacement curves generated with dilutions of acid–gel chromatography extracts of guinea-pig serum and rhIGF-I standards were parallel. Twenty-four, 3-week-old male guinea-pigs were treated with the IGF-I MAb, a bovine herpes virus-I (BHV-I) MAb (control MAb) or vehicle (phosphate-buffered saline) (n = 8 per group). Treatments were administered i.p. every 3 days for 24 days at a dose of 20 mg/kg body weight. Blood was obtained on day 23 (48 h after treatment) and on day 25 (24 h after treatment). In a liquid-phase assay, serum from the IGF-I MAb-treated group bound 38 ± 8% (mean ± s.e.m.) (day 23) and 56 ± 7% (day 25) of an 125I-labelled rhIGF-I trace at a final dilution of 1:10 000. Because of the development of an anti-mouse immune response in the guinea-pigs, these parameters would probably have been much greater during the first 2 weeks of the trial. Of the total IGF-I in serum, 50 ± 5% and 61±4% could be immunoprecipitated with an excess of rabbit anti-mouse immunoglobulin in samples from days 23 and 25 respectively. Comparisons between the groups treated with IGF-I MAb and BHV-I MAb revealed no significant differences in whole animal growth rate, growth of individual tissues, or pituitary GH content. Mean serum concentrations of IGF-I were 69 and 99% greater in IGF-I MAb-treated group than in the BHV-I MAb-treated group on days 23 and 25 respectively. These differences probably resulted from an extension of the half-life of IGF-I in serum of animals treated with the IGF-I MAb. The lack of effect of treatment with the IGF-I MAb suggests that local production of IGF-I is generally sufficient to maintain normal growth or that local production or activity of IGF-I is increased in a compensatory fashion. Journal of Endocrinology (1990) 124, 403–415

scholarly journals Insulin-Like Growth Factor (IGF)-I and Insulin in Normal and Growth-Restricted Mother/Infant Pairs

2007 ◽  
Vol 2007 ◽  
pp. 1-6 ◽  
Author(s):  
Ariadne Malamitsi-Puchner ◽  
Despina D. Briana ◽  
Dimitrios Gourgiotis ◽  
Maria Boutsikou ◽  
Karl-Philipp Puchner ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fetal Growth ◽  
Gestational Age ◽  
Insulin Like Growth Factor ◽  
Insulin Levels ◽  
Intrauterine Growth ◽  
Igf I ◽  
Appropriate For Gestational Age ◽  
Positive Correlations

Insulin-like growth factor (IGF)-I and insulin are essential for fetal growth. We investigated perinatal changes of both factors in 40 mothers and their 20 appropriate-for-gestational-age (AGA) and 20 intrauterine-growth-restricted (IUGR) fetuses and neonates on day 1 (N1) and day 4 (N4) postpartum. Fetal and N1, but not N4, IGF-I levels were increased in AGA (P<.001andP=.037, resp.). N1 insulin levels were lower in IUGR (P=.048). Maternal, fetal, and N1 IGF-I, and fetal insulin levels positively correlated with customized centiles (r=.374,P=.035,r=.608,P<.001,r=.485,P=.006, andr=.654,P=.021, resp.). Female infants presented elevated fetal and N4 IGF-I levels (P=.023andP=.016, resp.). Positive correlations of maternal, fetal, and neonatal IGF-I levels, and fetal insulin levels with customized centiles underline implication of both hormones in fetal growth. IUGR infants present gradually increasing IGF-I levels. Higher IGF-I levels are documented in females.

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