Mitochondria play a central role in energy metabolism. This process is regulated in part by specific mitochondrial proteins. These include cytochrome c, located in the mitochondrial inter-membrane space and the voltage-dependent anion channel (VDAC) located in the outer mitochondrial membrane (Kirk & Strange, 1998), which are involved in energy conversion, provision and apoptosis. Maternal nutrition during pregnancy plays an important role in determining mitochondrial protein abundance in the offspring (Budge et al. 2003). The extent to which such effects may be programmed in utero remain to be established. In the present study we examined the influence of maternal nutrient restriction over the period of placental growth on the abundance of these proteins in the fetal liver and lung.
Eighteen Welsh Mountain ewes of similar body weight and fat distribution were individually housed from 28 days of gestation. Six ewes were nutrient restricted (NR); these consumed 3.5 MJ of metabolisable energy (ME) per day (60 % of ME requirements for maintenance and growth of the conceptus) until 80 days gestation, with six controls (C) consuming 6.8-7.5 MJ day-1. After 80 days gestation, until near to term (term = 147 days), all animals were fed to appetite and consumed 8-10.9 MJ day-1. Tissues were sampled from 4-5 singleton fetuses from NR and C ewes at either mid- (80 days) and late (140 days) gestation after humane euthanasia (barbiturate overdose, 100 mg kg-1 pentobarbital sodium: Euthatal). Mitochondria were prepared and analysed by immunoblotting. Results (in arbitrary units) are presented as means ± S.E.M. Differences between nutritional groups were analysed using a Mann-Whitney U test.
Body and organ weights were similar between groups at either sampling age. In livers from NR fetuses cytochrome c abundance was significantly greater than C at 80 but not 140 days gestation. VDAC abundance between groups was similar but levels increased with gestational age. In the lung, however, cytochrome c abundance was lower in NR animals at 80 days gestation, but greater than C near to term when a similar trend was observed for VDAC.
In conclusion, maternal nutrient restriction in early fetal life has differential effects on mitochondrial protein abundance, which are tissue specific and only appear to result in persistent effects in the fetal lung.
D.P. Yakubu is supported by a University of Nottingham International Office Scholarship.