PC47 IMPACT OF MATERNAL UNDERNUTRITION DURING EARLY-MID GESTATION ON RESULTING ADULT OFFSPRING IN SHEEP

Abstract

Introduction: Suboptimal maternal nutrition during pregnancy is associated with increased risk of diseases in resulting adult offspring. Maternal undernutrition during placental growth produced a longer fetus at term with a disproportionately larger placenta and increased fat deposition. This study aimed to determine the long term consequences of early-mid gestation maternal undernutrition on blood pressure and plasma leptin concentration in young adult offspring. Methods: Seventeen male singleton bearing Scottish Black-face ewes of similar liveweight and body condition were individually housed from day of mating. Nine ewes were nutrient restricted (NR) consuming 4.0 MJ of metabolisable energy (ME) per day (50% ME requirements for maintenance and growth of conceptus) until 95 days gestation with 8 controls (C) consuming 8.0 MJ/day. After 95 days gestation until term (147 days) all ewes consumed 100% of requirements. At term lambs were delivered spontaneously and at 3 years old, the jugular vein and carotid artery were surgically catheterised for blood pressure (BP) measurement and blood sampling. Plasma was collected before and after a noradrenaline (NA) infusion with dose increases (2–48 ng/kg/min) at 10-minute intervals, and leptin concentration analysed. Animals were then humanely euthanased by barbiturate overdose to allow tissue sampling. Results are presented as mean ± standard error. Results: Between groups offspring body weight was similar at birth and 3 years of age but the NR group had larger fat (omental, perirenal and subcutaneous) deposits compared to controls. Basal BP prior to feeding was significantly higher in the NR offspring compared to controls (eg. diastolic 65 ± 3; NR 74 ± 2 mmHg (P<0.05)). Following NA infusion BP was similar between groups and rose with increasing NA concentration. With controls heart rate simultaneously decreased but this response was blunted in the NR group. The NR but not C offspring exhibited a significant increase in plasma leptin following NA infusion (C pre NA 3.22 ± 1.9; Post NA 3.16 ± 1.7; NR pre NA 3.47 ± 0.9; Post NA 4.5 ± 1.3 ng/ml (P<0.05)). Conclusion: Nutrient restriction between early-mid gestation produced hypertensive offspring with a blunted heart rate response to a vasoconstrictor challenge, with more fat and higher plasma leptin levels. Altering maternal nutrition during gestation may contribute to reprogramming of adult blood pressure and fat deposition contributing to hypertension and obesity in later life.