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.

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.

Effects of elevated blood insulin-like growth factor-I (IGF-I) concentration upon IGF-I in bovine mammary secretions during the colostrum phase

1993 ◽  
Vol 137 (2) ◽  
pp. 223-230 ◽  
Author(s):  
D. L. Hadsell ◽  
C. R. Baumrucker ◽  
R. S. Kensinger
Keyword(s):  
Growth Factor ◽  
Nutrient Restriction ◽  
Control Group ◽  
Insulin Like Growth Factor ◽  
Dry Period ◽  
Entire Treatment Period ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Serum Gh

ABSTRACT The objectives of these studies were to determine if the concentration of insulin-like growth factor-I (IGF-I) in mammary colostrum secretions could be altered through manipulation of IGF-I concentrations in blood and to compare the temporal changes of IGF-I in mammary secretions to those occurring for IgG1. Milking of 15 pregnant Holstein cows was stopped at 8 weeks prepartum and they were randomly assigned to one of three treatments. A control (C) treatment consisted of feeding the animals 100% of NRC requirements for protein and energy. A second group of cows was fed as the control group and injected with 1·8 μmol bovine GH/day. The third group was fed at 70% of NRC requirements for protein and energy to cause a moderate nutrient restriction (NR). Body weight was measured weekly. Blood was collected by tail venepuncture at 4 h intervals for 24 h. Mammary secretions were collected and pooled among contralateral front and rear quarters (diagonal) for measurement of volume, IGF-I and IgG1 concentrations. Samples were collected at −7, −5, −2, 0 and 1 week postpartum. Cows on the NR treatment failed to gain weight during the dry period compared with C cows (P < 0·05). Blood GH and IGF-I concentrations (P > 0·1) were unaffected by NR treatment. Cows treated with GH had higher (P < 0·01) serum GH and IGF-I levels throughout the entire treatment period, and higher serum IgG1 at 5 and 2 weeks prepartum (P < 0·01). Total mass of IGF-I secreted per diagonal averaged 3·6-fold greater for GH-treated cows during the prepartum period than C and NR cows (P < 0·01). The concentration of IGF-I in mammary secretions was not affected by treatment during the prepartum period, but was 40% greater (P < 0·05) in GH-treated cows than C and NR cows at parturition. Analysis of a selective index comparing IGF-I secretion with that of IgG1 suggested that IGF-I does not enter mammary secretions by passive diffusion from blood. Journal of Endocrinology (1993) 137, 223–230

Intravenous infusion of insulin-like growth factor I in fetal sheep reduces hepatic IGF-I and IGF-II mRNAs

1996 ◽  
Vol 271 (6) ◽  
pp. R1632-R1637 ◽  
Author(s):  
K. L. Kind ◽  
J. A. Owens ◽  
F. Lok ◽  
J. S. Robinson ◽  
K. J. Quinn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Intravenous Infusion ◽  
Feedback Inhibition ◽  
Fetal Liver ◽  
Plasma Concentrations ◽  
Insulin Like Growth Factor ◽  
Fetal Sheep ◽  
Igf I

Liver contains the highest concentrations of insulin-like growth factor (IGF) I mRNA in adult rats and sheep and is a major source of circulating IGF-I. In rats, inhibition of hepatic IGF-I production by exogenous IGF-I has been reported. In fetal sheep, skeletal muscle and liver are major sites of IGF-I synthesis and potential sources of circulating IGF-I. To determine whether feedback inhibition of IGF gene expression in fetal liver or muscle by IGF-I occurs, IGF-I and IGF-II mRNAs were measured in these tissues after intravenous infusion of recombinant human IGF-I into fetal sheep. Infusion of IGF-I (26 +/- 4 micrograms.h-1.kg-1; n = 6) or saline (n = 6) commenced on day 120 of pregnancy (term = 150 days) and continued for 10 days. Plasma concentrations of IGF-I were threefold higher in infused fetuses at 130 days of gestation (P < 0.0003), whereas those of IGF-II were unchanged. IGF-I infusion reduced the relative abundance of IGF-I mRNA (P < 0.0002) and IGF-II mRNA (P < 0.01) in fetal liver by approximately 50% but did not alter IGF-I or IGF-II mRNA in skeletal muscle. These results indicate that IGF-I inhibits the expression of both IGF-I and IGF-II genes in fetal liver and that IGF gene expression in fetal liver and muscle is differentially regulated by IGF-I.

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.

Regulation of gastrointestinal growth in fetal sheep by luminally administered insulin-like growth factor-I

1997 ◽  
Vol 152 (1) ◽  
pp. 29-38 ◽  
Author(s):  
J F Trahair ◽  
S J Wing ◽  
K J Quinn ◽  
P C Owens
Keyword(s):  
Small Intestine ◽  
Growth Factors ◽  
Gastrointestinal Tract ◽  
Growth Factor ◽  
Amniotic Fluid ◽  
Insulin Like Growth Factor ◽  
Fetal Sheep ◽  
Factor I ◽  
Proximal Small Intestine ◽  
Igf I

Abstract Fetuses swallow large volumes of amniotic fluid. Absence of swallowing results in gastrointestinal tract (GIT) growth deficits. While it is not yet known to what extent the growth factors present in amniotic fluid are involved in GIT ontogeny, milk-derived growth factors are considered to be important for neonatal growth. Our experiment tested the hypothesis that a luminal growth factor (insulin-like growth factor-I, IGF-I) can sustain or promote GIT growth in utero in a model of gastrointestinal tract growth retardation. Ten-day infusion of either human recombinant IGF-I or vehicle into twin fetal sheep at 80 days gestation via an indwelling esophageal catheter resulted in altered GIT growth. Weight of the forestomach and small intestine increased. Significant histological changes were noted in the proximal small intestine, i.e. the region most exposed to the luminal infusion. Mucosal tissues were reduced in size. While the enterocytes in the proximal small intestine were generally more mature with regard to the ontogeny of the apical endocytic complex (which is responsible for uptake and transport of whole peptides), there were also many abnormal cytological features present. These included the development of large lysosomal-like inclusion bodies and many surfactant-like particles within the apical cytoplasm. Plasma IGF-I levels were on average 20% higher in treated siblings, suggesting that luminal IGF-I crossed the fetal gut and entered blood. IGF-II levels were not significantly affected. These observations are consistent with the suggestion that growth factors, which are present in swallowed amniotic fluid, influence fetal ontogeny. Journal of Endocrinology (1997) 152, 29–38

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.

Sign in / Sign up

Export Citation Format

Share Document