The effect of chronic umbilical cord occlusion on uncoupling protein-2 (UCP2), voltage-dependent anion channel (VDAC) and cytochrome c protein abundance in the late gestation ovine fetal lung

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  • The effect of chronic umbilical cord occlusion on uncoupling protein-2 (UCP2), voltage-dependent anion channel (VDAC) and cytochrome c protein abundance in the late gestation ovine fetal lung

University of Cambridge (2004) J Physiol 555P, C95

Communications: The effect of chronic umbilical cord occlusion on uncoupling protein-2 (UCP2), voltage-dependent anion channel (VDAC) and cytochrome c protein abundance in the late gestation ovine fetal lung

M.G. Gnanalingham*, A. Mostyn†, M.E. Symonds*, D. Gardner*, D.A. Giussani‡ and T.J. Stephenson*

* Centre for Reproduction and Early Life, Institute of Clinical Research, University of Nottingham, †Department of Agricultural Science, Imperial College London Wye Campus and ‡Department of Physiology, University of Cambridge, Cambridge, UK

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Umbilical cord occlusion (UO) sufficient to restrict fetal blood supply by 30 % results in a range of fetal endocrine adaptations, including increased fetal plasma cortisol and premature maturation of mitochondria within brown adipose tissue (Gnanalingham et al. 2002). This study aimed to determine if UO results in changes in UCP2, VDAC and cytochrome c abundance within the fetal lung.

Nine ewes were entered into the study, which were all chronically instrumented under halothane anaesthesia with fetal vascular catheters. Five fetuses were then subjected to 3 days UO beginning at 125 days gestation by automated compression of the umbilical cord, with the remaining 4 acting as controls (C). At 137 ± 2 days gestation, all animals were humanely killed and fetal lungs dissected and frozen in liquid nitrogen. Total lung RNA was extracted, reverse transcribed and UCP2 mRNA abundance measured by RT-PCR using oligonucleotide primers designed specifically to ovine UCP2. The abundance of VDAC and cytochrome c mitochondrial proteins was determined by differential centrifugation and immunoblotting. The mRNA results are given as means and S.E.M. in arbitrary units, as a ratio of 18S rRNA and are expressed as a percentage of a reference sample, whilst the mitochondrial protein data are represented as a percentage of a reference sample. Statistical differences between groups were analysed by an unpaired Mann-Whitney U test (P < 0.05).

There were no significant differences in body (C 2.85 ± 0.23; UO 2.49 ± 0.10 kg) or lung (C 74.8 ± 2.0; UO 63.1 ± 6.0 g) weights between groups, although UO lungs had a tendency to be smaller. UO resulted in enhanced abundance of UCP2 mRNA (C 72.3 ± 3.0; UO 114.8 ± 5.4, P < 0.01), and mitochondrial VDAC (C 25.8 ± 0.9; UO 35.8 ± 1.7, P < 0.05), and cytochrome c (C 5.4 ± 0.7; UO 8.2 ± 0.4, P < 0.01) proteins.

In conclusion, chronic UO results in precocious maturation of lung mitochondria. These changes may be important in promoting gaseous exchange within the growth-restricted fetal lung, and may reflect an underlying susceptibility to infection in this group.

Where applicable, experiments conform with Society ethical requirements.

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