Effects of intrauterine insulin-like growth factor-1 therapy for fetal growth restriction on adult metabolism and body composition are sex specific.

Fetal growth restriction (FGR) is associated with compromised growth and metabolic function throughout life. Intrauterine therapy of FGR with intra-amniotic insulin-like growth factor-1 (IGF1) enhances fetal growth and alters perinatal metabolism and growth in a sex-specific manner, but the adult effects are unknown. We investigated the effects of intra-amniotic IGF1 treatment of FGR on adult growth and body composition, adrenergic sensitivity, and glucose-insulin axis regulation. Placental embolization-induced FGR was treated with four weekly doses of 360 µg intra-amniotic IGF1 (FGRI) or saline (FGRS). Offspring were raised to adulthood (18 mo: FGRI, n = 12 females, 12 males; FGRS, n = 13 females, 10 males) alongside offspring from unembolized and untreated sheep (CON; n = 12 females, 21 males). FGRI females had increased relative lean mass compared with CON but not FGRS (P < 0.05; 70.6 ± 8.2% vs. 61.4 ± 8.2% vs. 67.6 ± 8.2%), decreased abdominal adipose compared with CON and FGRS (P < 0.05; 43.7 ± 1.2% vs. 49.3 ± 0.9% vs. 48.5 ± 1.0%), increased glucose utilization compared with FGRS but not CON (P < 0.05; 9.6 ± 1.0 vs. 6.0 ± 0.9 vs. 7.6 ± 0.9 mg·kg-1·min-1), and increased ß-hydroxybutyric acid:nonesterified fatty acid ratio in response to adrenaline compared with CON and FGRS (P < 0.05; 3.9 ± 1.4 vs. 1.1 ± 1.4 vs. 1.8 ± 1.4). FGRS males were smaller and lighter compared with CON but not FGRI (P < 0.05; 86.8 ± 6.3 vs. 93.5 ± 6.1 vs. 90.7 ± 6.3 kg), with increased peak glucose concentration (10%) in response to a glucose load but few other differences. These effects of intra-amniotic IGF1 therapy on adult body composition, glucose-insulin axis function, and adrenergic sensitivity could indicate improved metabolic regulation during young adulthood in female FGR sheep.

Reduced cortisol and metabolic responses of thin ewes to an acute cold challenge in mid-pregnancy: implications for animal physiology and welfare.

BACKGROUND: Low food availability leading to reductions in Body Condition Score (BCS; 0 indicates emaciation and 5 obesity) in sheep often coincides with low temperatures associated with the onset of winter in New Zealand. The ability to adapt to reductions in environmental temperature may be impaired in animals with low BCS, in particular during pregnancy when metabolic demand is higher. Here we assess whether BCS affects a pregnant animal's ability to cope with cold challenges. METHODS: Eighteen pregnant ewes with a BCS of 2.7±0.1 were fed to attain low (LBC: BCS2.3±0.1), medium (MBC: BCS3.2±0.2) or high BCS (HBC: BCS3.6±0.2). Shorn ewes were exposed to a 6-h acute cold challenge in a climate-controlled room (wet and windy conditions, 4.4±0.1°C) in mid-pregnancy. Blood samples were collected during the BCS change phase, acute cold challenge and recovery phase. RESULTS: During the BCS change phase, plasma glucose and leptin concentrations declined while free fatty acids (FFA) increased in LBC compared to MBC (P<0.01, P<0.01 and P<0.05, respectively) and HBC ewes (P<0.05, P<0.01 and P<0.01, respectively). During the cold challenge, plasma cortisol concentrations were lower in LBC than MBC (P<0.05) and HBC ewes (P<0.05), and FFA and insulin concentrations were lower in LBC than HBC ewes (P<0.05 and P<0.001, respectively). Leptin concentrations declined in MBC and HBC ewes while remaining unchanged in LBC ewes (P<0.01). Glucose concentrations and internal body temperature (T(core)) increased in all treatments, although peak T(core) tended to be higher in HBC ewes (P<0.1). During the recovery phase, T4 concentrations were lower in LBC ewes (P<0.05). CONCLUSION: Even though all ewes were able to increase T(core) and mobilize glucose, low BCS animals had considerably reduced cortisol and metabolic responses to a cold challenge in mid-pregnancy, suggesting that their ability to adapt to cold challenges through some of the expected pathways was reduced.