Presented at the Neonatal Society 2002 Autumn Meeting.
Seetho W, Dandrea J, Mostyn A, Symonds ME, Stephenson T
Academic Division of Child Health, School of Human Development, University Hospital, Nottingham NG7 2UH
Introduction: Maternal nutrient restriction during early to mid gestation followed by adequate feeding up to term results in neonatal lambs with heavier kidneys that are narrower in width1 and subsequently exhibit increased mitochondrial abundance of cytochrome c at six months of age2. The following study therefore aimed to determine whether nutrient restriction in late gestation may reprogram kidney growth and mitochondrial protein abundance for either voltage dependent anion channel (VDAC) and cytochrome c. Both these proteins have a role in regulating mitochondrial energy metabolism.
Methods: Thirteen primiparous twin pregnant Border Leicester cross Swaledale ewes were entered into the study. Six ewes were allocated to the control (C) group and consumed 100% of total metabolisable energy (ME) requirements (for both ewe maintenance and growth of the conceptus in order to produce a 4.5 kg lamb at term). The remaining seven ewes were nutrient restricted (NR) and consumed 60% of total ME requirements. All ewes lambed normally at term, and one twin was euthanased with an overdose of barbiturate within 6 hours of birth to enable kidney sampling with the remaining twin being reared with its ewe until 30 d after birth. Kidneys were weighed and measurements taken of length, breadth and width (see table below). Mitochondria were also prepared from each kidney and abundance of VDAC and cytochrome c determined by immunoblotting. Differences in nutritional treatments were analysed using a Mann-Whitney U-test.
Results: There was no difference in kidney weights between groups at either age, but lambs born to NR ewes exhibited a trend to have smaller kidneys that had significantly reduced width at birth and a smaller breadth at one-month. The abundance of VDAC and cytochrome c was unaffected by maternal nutrition but cytochrome c concentration was negatively correlated with kidney mass at 30 days in NR, but not C offspring (C: r2 = 0.029; NR: r2 = 0.96 (P<0.01)).
Significantly different from NR: * P<0.05, ** P<0.01
Conclusion: In contrast to the effect of maternal nutrient restriction earlier in gestation, reduced maternal food intake in late gestation restricted kidney growth and may have contributed to increased mitochondrial activity in those NR offspring that had small kidneys one-month after birth.
References
1. Whorwood CB, Firth KM, Budge H, Symonds ME. Endocrinology 2001; 142, 2854-2864.
2. Gopalakrishnan G, Seetho IW, Robinson A, Mostyn A, Pearce S, Dandrea J, Wilson V, Ramsay MM, Stephenson T, Symonds ME. Proc Nutr Soc 2002 (In press).