A model of intrauterine growth retardation caused by chronic maternal undernutrition in the rat: effects on the somatotrophic axis and postnatal growth

Abstract

While it is well established that severe maternal undernutrition during pregnancy causes intrauterine growth retardation (IUGR), there has been relatively little study of the endocrine consequences and postnatal development of growth-retarded offspring. We have developed a model in the rat of IUGR by nutritional restriction of the mother throughout gestation and have examined the effects of fetal growth retardation on the endocrine and metabolic status during the perinatal period. Timed matings were performed in Wistar rats and dams were randomly assigned to one of two dietary treatment groups. Food was available ad libitum throughout pregnancy to a control group (at libitum group) and a restricted group was fed 30% of the ad libitum intake (restricted fed group). After birth, food was available ad libitum in both groups and litter size was adjusted to eight pups per litter. Dams lost a significant amount of body weight throughout gestation due to undernutrition but were able to catch up to the ad libitum group by day 10 postnatally. Litter size was not affected by maternal undernutrition. Maternal plasma IGF-I levels were significantly reduced in the restricted fed group throughout gestation (P < 0.001) but were not different postnatally. Maternal plasma IGF-binding proteins (IGFBPs)-1, -2 and -3 were significantly (P < 0.05) increased in the restricted fed dams. The mean body weights of fetuses in late gestation from the restricted fed dams were significantly lower (P < 0.001) in comparison with fetuses from control dams. Placental weights were also significantly (P < 0.01) reduced in the restricted fed compared with control dams. Body weights were significantly lower in the offspring of restricted fed dams than control dams from birth (P < 0.01) until 90 days of age (P < 0.05). Nose-rump length was reduced in the fetuses of the restricted fed group at day 22 of gestation (P < 0.001) until weaning (P < 0.05). Plasma IGF-I levels were significantly reduced in the pups of restricted fed dams from day 22 of gestation (P < 0.01) until postnatal day 9 (P < 0.05) but were not significantly different at the later time-points. Plasma insulin levels were significantly reduced in the pups of restricted fed dams at birth (P < 0.05) but not at later time-points. Plasma IGFBP-1 and -2 levels were significantly increased in the offspring from restricted fed dams at day 22 of gestation, at birth and at day 9 postnatally (P < 0.05). 125I-Bovine GH specific binding to liver membranes was significantly lower (P < 0.05) in offspring from restricted fed dams at 21 days of age but not at 90 days of age. These data demonstrate that nutritional deprivation in the pregnant rat leads to IUGR and postnatal growth failure and to changes in allometric growth patterns and endocrine parameters of the somatotrophic axis postnatally.

Effect of Food Restriction on Ghrelin in Normal‐Cycling Female Rats and in Pregnancy

“…It is well known that metabolic adaptations to undernutrition are linked to changes in the endocrine environment (11). We have used a chronic food-restriction model in normal-cycling female rats and a maternal nutritional restriction throughout pregnancy as an experimental approach to study the effect of long-term undernutrition on circulating ghrelin levels and gastric ghrelin mRNA expression.…”

“…The degree of food restriction had been determined according the experimental set previously described (11). The rats were weighed every 3 days from the beginning of the experiment until they were killed.…”

Adult growth hormone treatment reduces hypertension and obesity induced by an adverse prenatal environment

“…However, while some studies report GHD and decreased plasma IGF-I concentrations (Woodall et al 1996, Albertsson-Wikland et al 1998, others report resistance to GH, IGF-I and/or insulin in the presence of normal GH, IGF-I and insulin profiles (Gluckman & Harding 1997, Chatelain et al 1998. Furthermore, it has been shown that GH secretion, either spontaneous or evoked, is blunted in obesity (Scacchi et al 1999).…”

“…We have developed an animal model of fetal programming by maternal undernutrition throughout gestation, generating a nutrient-deprived intrauterine environment that results in fetal growth retardation and postnatal growth failure, and leads to changes in allometric growth patterns and endocrine parameters of the somatotrophic axis (Woodall et al 1996). Our model closely resembles the clinical and metabolic abnormalities seen in humans born at low birth weight and, furthermore, displays the phenotype of syndrome X (Reaven 1993, Smith et al 1999.…”

Programming of obesity and cardiovascular disease

“…Calorie restriction has been found to either decrease or not IGF levels at birth and to increase or not IGF binding proteins (IGFBPs). 55,56 Protein restriction decreased plasma IGF-1 levels in the progeny at birth, 57,58 as well as augmented the abundance of IGFBP-1 and -2, the liver production of which being regulated in part by insulin and glucocorticoids. 58 A third pathway of generating obesity in children and adult is a modification in the population of fat cell precursors.…”