A model of intrauterine growth retardation caused by chronic maternal undernutrition in the rat: effects on the somatotrophic axis and postnatal growth.
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.
Woodall
S M
SM
Research Centre for Developmental Medicine and Biology, University of Auckland, New Zealand.
Breier
B H
BH
Johnston
B M
BM
Gluckman
P D
PD
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D001835:Body Weight; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000209:etiology*; D013006:Growth Hormone / Q000378:metabolism; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D009748:Nutrition Disorders / Q000097:blood / Q000150:complications*; D009929:Organ Size; D010920:Placenta / Q000033:anatomy & histology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone