Periconceptional Undernutrition Alters Growth Trajectory and Metabolic and Endocrine Responses to Fasting in Late-Gestation Fetal Sheep

Maternal undernutrition during pregnancy can lead to impaired metabolic regulation in postnatal offspring. The extent to which such abnormalities are determined in early gestation, and may already be present in fetal life, is unknown. We studied the effect of periconceptional undernutrition on fetal growth and metabolism in late gestation. Ewes were either well fed throughout pregnancy (N) or undernourished to reduce ewe weight by 15% from 61 d before until 30 d after mating (UN). At 121 d, one cohort of ewes and their singleton fetuses (N, n = 10; UN, n = 10) were fasted for 72 h, given 25 g of glucose i.v. over 8 h, and refed. Fetal and placental weights were not different at 131 d. UN ewes had higher glucose, amino nitrogen, and Hb concentrations than N ewes. UN fetuses had higher glucose and lactate, and lower amino nitrogen and O2 concentrations and pH. UN ewes had higher insulin and lower IGF-I concentrations, and UN ewes and fetuses had higher placental lactogen concentrations. A second cohort (N, n = 8; UN, n = 10) were studied until term. Chest girth increment was reduced in UN fetuses until delivery, but birth weights were not significantly reduced. These findings suggest that fetal growth, metabolic and endocrine status, and placental function in late gestation are influenced by maternal nutrition in the periconceptional period, independent of fetal size. Metabolic and endocrine adaptations in the mother may mediate some of these effects. Such adaptations may allow continued fetal growth and survival in the face of a potentially adverse nutritional environment.