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Maternal undernutrition during early to mid pregnancy and programming of mitochondrial uncoupling protein-2 (UCP2) and voltage-dependent anion channel (VDAC) in the juvenile lung

Presented at the Neonatal Society 2003 Summer Meeting (programme).

Gnanalingham GM1, Yakubu DP1, Gopalakrishnan GS1, Mostyn A1, Alves-Guerra MC2, Pecqueur C2, Miroux B2, Symonds ME1, Stephenson T1

1 Academic Division of Child Health, School of Human Development, University Hospital, Nottingham NG7 2UH, UK
2 CNRS-UPR9078 faculté de Médecine Necker Enfants-Malades 156 rue de Vaugirard 75730 Paris, France

Introduction: Mitochondria are involved in cellular energy metabolism and can regulate apoptosis. Voltage-dependent anion channel (VDAC), together with uncoupling protein-2 (UCP2) may regulate reactive oxygen species within mitochondria. The absence of UCP2 may actually be protective against the adverse effects of infection (1). Maternal nutrition through pregnancy plays an important role in determining mitochondrial protein abundance during postnatal development (2). However, the extent to which nutritional manipulation affects UCP2 and VDAC abundance in the juvenile lung has yet to be established.

Methods: Twelve Welsh Mountain ewes of similar age, body weight and fat distribution were individually housed from 28 days 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 d gestation, with six controls (C) consuming 6.8-7.5 MJ/day. After 80 d gestation, until term (147 d), all animals consumed 6.8-7.5 MJ/day, sufficient to fully meet their ME requirements. Lambs were delivered spontaneously and each ewe raised a single lamb that was weaned at 6 weeks of age. At 6 months of age all lambs were euthanased (100mg kgˉ¹ pentobarbital sodium: Euthatal) to enable tissue sampling. Mitochondrial fractions were prepared and protein abundance was determined by immunoblotting. Results (as % of a reference sample run on all gels) are presented as means with their standard errors (SEM).

Results: Lung fresh and dry weights and total protein concentration were similar between nutritional groups. UCP2 (C 98.8 ± 2.0; NR 32.4 ± 2.1, p<0.05 Mann-Whitney U test) and VDAC (C 18 ± 0.8; NR 8 ± 1.5, p<0.01) abundance were significantly lower in the NR group at 6 months postnatal age.

Conclusions: In conclusion, the decreased UCP2 and VDAC abundance in the juvenile lung following maternal undernutrition, is likely to have a pronounced effect on mitochondrial function. This may be critical during infection.

1. Arsenijevic D, Onuma H, Pecqueur C, Raimbault S, Miroux B, Couplan E et al. Nat Genet 2000; 26: 435-39.
2. Mostyn A, Wilson V, Dandrea J, Yakubu DP, Budge H, Alves-Guerra MC et al. British Journal of Nutrition 2003 (In press).

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