Nutritional paradigms of ovine fetal growth restriction: implications for human pregnancy

Low birth weight and prematurity are associated with short inter-pregnancy intervals, low pre-pregnancy weights, insufficient maternal weight gains during pregnancy, multifetal pregnancies and a young maternal age. Improvements in maternal nutritional status are arguably imperative for ensuring an appropriate pregnancy outcome in these vulnerable groups, but ethical boundaries limit these investigations. Experimental paradigms using the pregnant sheep have been widely used to identify the nutritionally sensitive periods of conceptus development. In adult sheep, severe undernutrition during the periconceptual period accelerates maturation of the fetal hypothalamic-pituitary adrenal axis and results in pre-term delivery. Low pre-pregnancy weight, followed by undernutrition during mid-pregnancy, results in reduced placental growth and lower birth weights at term. Studies that have restricted nutrients during mid-gestation only reveal variable effects on the placental and fetal growth trajectory, however if undernutrition is prolonged during late-pregnancy, fetal growth is compromised, particularly in twin pregnancies. In contrast, overnourishing the adolescent sheep to promote rapid maternal growth, results in the premature delivery of low birth weight lambs. These effects are mediated by impaired placental growth, uteroplacental blood flows and fetal nutrient uptakes. At the other end of the nutritional spectrum, undernourishing the adolescent sheep to gradually deplete nutrient reserves, results in fetal growth restriction which is independent of alterations in placental mass.