title: Chronic umbilical cord compression results in accelerated maturation of lung and brown adipose tissue in the sheep fetus during late gestation.
abstract: 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 11beta-hydroxysteroid dehydrogenase (11beta-HSD)1 and -2 mRNA, and mitochondrial protein voltage-dependent anion channel (VDAC) and cytochrome c in these tissues. At 118 +/- 2 days of gestation (dGA; term approximately 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-h episodes of hypoxemia at 130 +/- 1 and 134 +/- 1 dGA before tissue sampling at 137 +/- 2 dGA. In both tissues, UCC upregulated UCP2 and GR mRNA, plus VDAC and cytochrome c mitochondrial proteins. In lung, UCC increased 11beta-HSD1 mRNA but decreased 11beta-HSD2 mRNA abundance, a pattern reversed for BAT. UCC increased UCP1 mRNA and its translated protein in BAT. UCP2, GR, 11beta-HSD1 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.
authors.affiliation: Centre for Reproduction and Early Life, Institute of Clinical Research, University of Nottingham, Nottingham NG7 2UH, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Gnanalingham
authors.forename: D A
authors.initials: DA
authors.lastname: Giussani
authors.forename: P
authors.initials: P
authors.lastname: Sivathondan
authors.forename: A J
authors.initials: AJ
authors.lastname: Forhead
authors.forename: T
authors.initials: T
authors.lastname: Stephenson
authors.forename: M E
authors.initials: ME
authors.lastname: Symonds
authors.forename: D S
authors.initials: DS
authors.lastname: Gardner
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics; D002001:Adipose Tissue, Brown / Q000098:blood supply / Q000196:embryology* / Q000502:physiology; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics; D002908:Chronic Disease; D005260:Female; D005333:Fetus / Q000098:blood supply; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006153:Guanosine Diphosphate / Q000378:metabolism; D006728:Hormones / Q000097:blood; D007473:Ion Channels; D008168:Lung / Q000098:blood supply / Q000196:embryology* / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D008928:Mitochondria / Q000502:physiology; D024101:Mitochondrial Proteins / Q000235:genetics; D010100:Oxygen / Q000097:blood; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000235:genetics; D012756:Sheep; D014470:Umbilical Cord / Q000503:physiopathology*; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2
chemical_list: D002352:Carrier Proteins; D006728:Hormones; D007473:Ion Channels; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D002245:Carbon Dioxide; D006153:Guanosine Diphosphate; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D010100:Oxygen