Elevating Maternal Insulin-Like Growth Factor-I in Mice and Rats Alters the Pattern of Fetal Growth by Removing Maternal Constraint

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 less than 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 (10 micrograms 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 (1 microgram/g body weight per day), bovine GH (bGH; 0.6 microgram/g body weight per day) or saline from day 1 to 19 of pregnancy. IGF-I therapy but not bGH or saline abolished (P less than 0.01) maternal constraint and altered (P less than 0.01) the relationship between placental and fetal weight. When high or low IGF-I line mice embroys were transplanted into a normal line of mice, the expected negative relationship (P less than 0.05) between mean fetal weight and litter size was maintained. However, the embryos of the high line were heavier (P less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin-like growth factor levels during pregnancy in the cow are affected by protein supplementation in the maternal diet

“…Studies in rats and mice (Gluckman et al, 1992) have shown that maternal IGF I affects foetal growth by altering some aspects of placental function. Unfortunately, placental production and transfer of IGF was unable to be measured in this study.…”

“…IGF I appears to be particularly sensitive to dietary protein levels during second trimester of gestation. Considering the importance of IGF concentrations in the development of the foetus (Gluckman et al, 1992;Brameld et al, 2000), these may represent one of the mechanisms by which foetal development is affected by protein levels in pasture. From our studies, the level of protein in the diet that can be produced by medic pasture is clearly sufficient to influence IGF concentrations in the heifers.…”

“…Treatment of rodents with IGF I overcomes maternal constraints on foetal growth and alters the usual close correlation between foetal and placental size (Gluckman et al, 1992) and suggests that maternal IGF I directly or indirectly affects placental function (Gluckman and Harding, 1994). Kind et al (1995) showed that restriction of placental growth reduces circulating levels of IGF I in the sheep foetus and reduces the capacity for the production of IGF I in a number of tissues suggesting that altered production of IGF I in various tissues may contribute to retarded foetal growth.…”

Proline, Leucine, and Alanine Transport in Placental Microvillous Membrane Vesicles Prepared from Late Gestational Rats.

“…The PMV was resuspended in HEPES-sucrose buffer (300 mM sucrose in 10 mM HEPES-Tris-base buffer, pH 7.4) by passing it 20 times through a 25-gauge needle, It has been widely accepted that the supply of amino acids from mother to fetus is of crucial importance for fetal growth and development. In vitro study, the treatment with growth factors, such as epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) resulted in fetal growth [3,8,10], increased amino acid uptake in cultured placental cells [15,18,21]. The serum levels of amino acid are known to be kept higher in the fetal side than those in maternal side in human [5] and also in rats [3], indicating an active transport across the placental microvillous membrane [14].…”

Birth weight effect in twin‐born lambs from mid‐pregnancy shearing is associated with changes in maternal IGF‐I concentration

“…In humans, a positive correlation between foetal IGF-I concentration at term and birth mass has been reported (Gluckman et al 1983). Similarly, in genetically divergent IGF-I lines of mice, high IGF-I line mice display heavier foetal weights (Kroonsberg et al 1989), and administration of IGF-I in pregnant mice has also been shown to remove the negative correlation between foetal weight and litter size (Gluckman et al 1992). Conversely, in sheep, divergent selection based on circulating plasma IGF-I concentrations has resulted in unexpectedly lower birth weights in the high IGF-I line in comparison to the low line (Blair et al 2002;Kenyon et al 2007).…”