Maternal nutrient restriction during the period of rapid placental growth (30-80 days) followed by adequate feeding up to term results in normal sized fetuses with a larger placenta in which the normal relationship between plasma insulin-like growth factor (IGF)-I and body conformation is lost (Heasman et al. 2000). IGFII and -I are synthesised primarily by the liver and are essential for normal fetal and postnatal growth and development, respectively, but the extent to which they may be nutritionally programmed after birth has not been examined. The aim of the present study was to determine whether maternal nutrient restriction during early to mid-gestation can result in altered hepatic IGF mRNA abundance in the resulting offspring.

Twelve singleton-bearing Welsh Mountain ewes of similar age, weight, and body condition score were entered into the study and individually housed from 28 days gestation. Six ewes were fed a nutrient restricted (NR) diet (3.5 MJ day^-1) until 80 days gestation, whilst the remaining ewes were fed a control (C) diet 6.8-7.5 MJ day^-1. After 80 days gestation, until term (147 days), all ewes received (6.8-7.5 MJ day^-1), sufficient to fully meet their metabolisable energy (ME) requirements to produce a 4.5 kg lamb at term. Lambs were born spontaneously, and at 6 months of age, all animals were humanely euthanased (100 mg kg^-1 pentobarbital sodium: Euthatal, I.V.), to enable liver tissue sampling. All procedures were carried out according to UK legislation. Tissue samples collected were stored at -70 °C until molecular analysis. Total RNA was extracted from liver tissue, reverse transcribed and abundance of IGF-1, and IGF-2 mRNA was measured by RT-PCR using oligonucleotide primers specific to ovine IGF-1 (forward 5Ô-CCCATCTCCCTGGATTTCTT-3Ô and reverse 5Ô-ACATCTCCAGAATCCTCAGA-3Ô) and IGF-2 (forward 5Ô-TCACAGCAGGAAAGTCTATG-3Ô and reverse 5Ô-GGCACAGTAAGTCTCCAGCA-3Ô). Results are given as means ± S.E.M. in arbitrary units as a ratio of 18S rRNA and are expressed as a percentage of a reference sample present on all gels. Statistical differences between nutritional groups were analysed using a Mann-Whitney U test.

There were no significant differences in growth, body or liver weights between C and NR offspring up to 6 months of age. The abundance of IGF-II (C 51 ± 8 a.u; NR 112 ± 21 a.u (P < 0.05)) but not IGF-I (C 115 ± 36 a.u; NR 145 ± 30 a.u) mRNA was higher in livers of NR offspring.

The increased hepatic IGF-II mRNA in NR compared with C offspring may represent an adaptation to nutrient restoration after 80 days gestation. It did not, however, contribute to any immediate change in juvenile growth but may be important in regulating endocrine adaptations during subsequent periods of nutrient deprivation.

M.A. Hyatt was supported by a University of Nottingham Postgraduate Scholarship and by the Children’s Brain Tumour Research Campaign.