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1 Centre for Reproduction and Early Life, University of Nottingham, Nottingham, United Kingdom
2 The Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom
* To whom correspondence should be addressed. E-mail: michael.symonds{at}nottingham.ac.uk.
Umbilical cord compression (UCC) sufficient to reduce umbilical blood flow by 30% for 3 days, results in increased fetal plasma cortisol and catecholamines that are likely to promote maturation of the fetal lung and brown adipose tissue (BAT). We determined the effect of UCC on the abundance of uncoupling protein (UCP) 1 (BAT only) and 2, glucocorticoid receptor (GR) and 11
-hydroxysteroid dehydrogenase (11
HSD) type 1 and 2 mRNA,and mitochondrial proteins voltage - dependent anion channel (VDAC) and cytochrome c in these tissues. At 118 ± 2 days of gestation (dGA; term ~145 days), 14 fetuses were chronically instrumented. Eight fetuses were then subjected to 3 days of UCC from 125 dGA and the remaining fetuses were sham-operated. All fetuses were then exposed to two 1-hour episodes of hypoxemia at 130 ± 1 and 134 ± 1 dGA, before tissue sampling at 137 ± 2 dGA. In both tissues, UCC up-regulated UCP2 and GR mRNA, plus VDAC and cytochrome c mitochondrial proteins. In lung, UCC increased 11
HSD1 mRNA but decreased 11
HSD2 mRNA abundance, a pattern reversed for BAT. UCC increased UCP1 mRNA and its translated protein in BAT. UCP2, GR, 11
HSD types 1 and 2 mRNA, plus VDAC and cytochrome c protein abundance were all significantly correlated with fetal plasma cortisol and catecholamine levels, but not thyroid hormone concentrations, in the lung and BAT of UCC fetuses. In conclusion, chronic UCC results in precocious maturation of the fetal lung and BAT mitochondria, an adaptation largely mediated by the surge in fetal plasma cortisol and catecholamines that accompanies UCC.
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