Maternal nutrient restriction during early to mid gestation alters the relationship between insulin-like growth factor I and bodyweight at term in fetal sheep

The present study was designed to determine whether altered placental size, as a consequence of maternal nutrient restriction in sheep between 28 and 77 days gestation, is associated with a modified relationship between fetal weight or dimensions and plasma insulin-like growth factor (IGF) I concentration or abundance of hepatic IGF-I and IGF-II mRNA close to term. Singleton-bearing ewes consumed either 1.2x (controls, n = 19) or 0.5x (nutrient restricted. n = 28) their metabolizable energy (ME) requirements from 28 to 77 days gestation, after which all ewes were fed in order to fully meet their ME requirements for maintenance and pregnancy. Close to term (145 +/- 1 days) plasma IGF-I concentration in cord blood was similar between groups, but only significantly correlated with fetal bodyweight, thoracic circumference, crown-rump length and lean body mass in lambs born to control (r(2) = 0.38, 0.76, 0.33. 0.42; P < 0.001), and not to nutrient-restricted (r(2) = 0.01, 0.11, 0.01, 0.02) ewes. There were no differences in fetal hepatic expression of IGF-I and IGF-II mRNA between groups close to term. In conclusion., maternal nutrient restriction in early to mid gestation followed by feeding to requirements up to term alters the relationship between fetal IGF-I, bodyweight and length. Increasing maternal nutrition in later gestation after a prolonged period of nutrient restriction may stimulate fetal nutrient supply such that fetal growth is enhanced without an increase in plasma IGF-I. As a result, there is a loss of the relationship between fetal weight and plasma IGF-I concentration observed in fetuses whose mothers are fed adequately throughout gestation.