Nutrition and fetal growth: paradoxical effects in the overnourished adolescent sheep

Inappropriate maternal nutrient intake at key developmental timepoints duri ng ovine pregnancy has a profound influence on the outcome of pregnancy and aspects of postnatal productivity. However, the responses to alterations i n maternal nutrition in adult sheep are often highly variable and inconsist ent between studies. The growing adolescent sheep provides a new, robust an d nutritionally sensitive paradigm with which to study the causes, conseque nces and reversibility of prenatal growth restriction. Overnourishing the a dolescent dam to promote rapid maternal growth throughout pregnancy results in a major restriction in placental mass, and leads to a significant decre ase in birthweight relative to moderately fed, normally growing adolescents of equivalent gynaecological age. Maternal insulin and IGF-I concentration s are increased from an early stage of gestation in overnourished adolescen t dams and these hormones ensure that the anabolic drive required to promot e maternal tissue synthesis is initiated at a time when the nutrient requir ements of the gravid uterus are low. The major restriction in fetal growth in rapidly growing darns occurs irrespective of high concentrations of esse ntial nutrients in the maternal circulation and suggests that the small siz e or altered metabolic and transport capacity of the placenta is the primar y constraint to fetal growth. The decrease in placental weight in the overn ourished animals reflects a significant reduction in both fetal cotyledon n umber and mean cotyledon weight. The role of nutritionally mediated alterat ions in progesterone and the components of the IGF system in this early pre gnancy placental phenomenon are being investigated. Nutritional switch-over studies have demonstrated that reducing maternal nutrient intake at the en d of the first third of pregnancy can stimulate placental growth and enhanc e pregnancy outcome, but increasing nutrient intake at this time has a dele terious effect on placental development and fetal growth.