An adverse prenatal environment may induce long-term metabolic consequences, in particular obesity and insulin resistance. Although the mechanisms are unclear, this programming has generally been considered an irreversible change in developmental trajectory. Adult offspring of rats subjected to undernutrition during pregnancy develop obesity, hyperinsulinemia, and hyperleptinemia, especially in the presence of a high-fat diet. Reduced locomotor activity and hyperphagia contribute to the increased fat mass. Using this model of maternal undernutrition, we investigated the effects of neonatal leptin treatment on the metabolic phenotype of adult female offspring. Leptin treatment (rec-rat leptin, 2.5 microg/g.d, sc) from postnatal d 3-13 resulted in a transient slowing of neonatal weight gain, particularly in programmed offspring, and normalized caloric intake, locomotor activity, body weight, fat mass, and fasting plasma glucose, insulin, and leptin concentrations in programmed offspring in adult life in contrast to saline-treated offspring of undernourished mothers who developed all these features on a high-fat diet. Neonatal leptin had no demonstrable effects on the adult offspring of normally fed mothers. This study suggests that developmental metabolic programming is potentially reversible by an intervention late in the phase of developmental plasticity. The complete normalization of the programmed phenotype by neonatal leptin treatment implies that leptin has effects that reverse the prenatal adaptations resulting from relative fetal undernutrition.

To determine the effects of chronic maternal undernutrition on postnatal somatic growth and blood pressure, pregnant dams were randomly assigned to one of two dietary treatment groups. A control group was fed ad libitum throughout pregnancy and a restricted group was fed 30% of ad libitum intake. From birth, feeding was ad libitum in both groups, and litter size was adjusted to eight pups per litter. Litter size was not significantly altered by the reduced maternal intake. Offspring of the restricted fed group were significantly smaller than offspring from the ad libitum fed group from birth until 12 wk of age, but by 30 wk had similar body weights. Blood pressure was measured by tail cuff plethysmography. Offspring from the restricted fed group were found to have significantly (p < 0.05) elevated systolic blood pressure (5-8 mm Hg) at 30, 48, and 56 wk of age. These data demonstrate that nutritional deprivation in the pregnant rat leads to changes in postnatal allometric growth patterns, to delayed catch-up growth, and to elevated blood pressure in adulthood. The data are consistent with the hypothesis that poor maternal nutrition in pregnancy may irreversibly alter programming of the development of cardiovascular homeostasis.

This report describes essential requirements for the validation of a radioimmunoassay (RIA)

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.

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An adverse prenatal environment may induce long-term metabolic consequences, in particular obesity, hyperleptinemia, insulin resistance, and type 2 diabetes. Although the mechanisms are unclear, this "programming" has generally been considered an irreversible change in developmental trajectory. Adult offspring of rats subjected to undernutrition (UN) during pregnancy develop obesity, hyperinsulinemia, and hyperleptinemia, especially in the presence of a high-fat diet.