Maternal nutrition alters the expression of insulin-like growth factors infetal sheep liver and skeletal muscle

We investigated the influence of maternal dietary restriction between days 28 and 80 of gestation followed by re-feeding to the intake of well-fed ewe s up to 140 days of gestation (term is 147 days) in sheep, on expression of mRNA for insulin-like growth factor (IGF)-I, IGF-II and growth hormone rec eptor (GHR) in fetal liver and skeletal muscle. Singleton bearing ewes eith er consumed 3.2-3.8 MJ/day of metabolisable energy (ME) (i.e. nutrient rest ricted - approximately 60% of ME requirements, taking into account requirem ents for both ewe maintenance and growth of the conceptus) or 8.7-9.9 MJ/da y (i.e. well fed - approximately 150% of ME requirements) between days 28 a nd 80 of gestation. All eu es were then well fed (150% of ME requirements) up to day 140 of gestation and consumed 8-10.9 MJ/day. At days 80 and 140 o f gestation, five ewes were sampled from each group and fetal tissues taken . There was Ilo difference in fetal body weight or liver weights between gr oups at either sampling date, or skeletal muscle (quadriceps) weight: at 14 0 days. IGF-I mRNA abundance was lower in livers of nutrient-restricted fetuses at day 80 of gestation (nutrient restricted 2.35; well fed 3.70 arbitrary unit s), but was higher than well-fed fetuses at day 140 of gestation, after 60 days of re-feeding (restricted/re-fed 4.27; well fed 2.83; S.E.D. 0.98 arbi trary units, P=0.061 for diet x age interaction). IGF-II mRNA abundance was consistently higher in livers of nutrient-restricted fetuses (80 clays: nu trient restricted 7.78; well fed 5.91; 140 days: restricted/re-fed 7.23; we ll fed 6.01; S.E.D. 1.09 arbitrary units, P=0.061 for diet). Nutrient restr iction had no effect on hepatic GHR mRNA abundance, hut re-feeding of previ ously nutrient-restricted fetuses increased GHR mRNA compared with continuo usly well-fed fetuses (80 days: nutrient restricted 70.6; well fed 75.1; 14 0 days: restricted/re-fed 115.7; well fed 89.4, S.E.D. 10.13 arbitrary unit s, P = 0.047 for diet x age interaction). In fetal skeletal muscle, IGF-I m RNA abundance was not influenced by maternal nutrition and decreased with g estation age (P<0.01). IGF-II mRNA abundance was higher in skeletal muscle of nutrient-restricted fetuses compared with well-fed fetuses at day 80 of gestation (nutrient restricted 16.72; well fed 10.53 arbitrary units), but was lower than well-fed fetuses after hn days of re-feeding (restricted/re- fed 7.77; well fed 13.72, S.E.D. 1.98 arbitrary units, P<0.001 fur dirt x a ge interaction). There was no effect of maternal nutrition or gestation age on fetal skeletal muscle GHR expression. In conclusion, maternal nutrient restriction in early to mid gestation with re-feeding thereafter results in alterations in hepatic and skeletal muscle expression of IGF-I, IGF-II and /or GHR in the fetus which may subsequently relate to altered organ and tis sue function.