title: Growth inhibition and compensation in response to neonatal hypoxia in rats.
abstract: BACKGROUND
  Hypoxia (Hx) is an important disease mechanism in prematurity, childhood asthma, and obesity. In children, Hx results in chronic inflammation.
  
  
  METHODS
  We investigated the effects of Hx (12% O2) during postnatal days 2-20 in rats. Control groups were normoxic control (Nc), and normoxic growth restricted (Gr) (14-pup litters).
  
  
  RESULTS
  The Hx-exposed and Gr rats had similar decreases in growth. Hx increased plasma tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) levels and decreased insulin-like growth factor 1 (IGF-I) and vascular endothelial growth factor (VEGF) levels. Hx resulted in hypertrophy of the right ventricle (RV) but disproportionate decrements in limb skeletal muscle (SM) growth. miR-206 was depressed in the hypertrophied RV of Hx rats but was increased in growth-retarded SM. Hx resulted in decreased RV messenger RNA (mRNA) level for myostatin but had no effect on SM myostatin. The mRNA for Hx-sensitive factors such as hypoxia inducible factor-1α (HIF-1α) was depressed in the RV of Hx rats, suggesting negative feedback.
  
  
  CONCLUSIONS
  The results indicate that Hx induces a proinflammatory state that depresses growth-regulating mechanisms and that tissues critical for survival, such as the heart, can escape from this general regulatory program to sustain life. This study identifies accessible biomarkers for evaluating the impact of interventions designed to mitigate the long-term deleterious consequences of Hx that all too often occur in babies born prematurely.
authors.affiliation: Department of Pediatrics, Pediatric Exercise Research Center, University of California, Irvine, Irvine, California, USA. saizik@uci.edu
authors.forename: Shlomit
authors.initials: S
authors.lastname: Radom-Aizik
authors.forename: Frank P
authors.initials: FP
authors.lastname: Zaldivar
authors.forename: Dwight M
authors.initials: DM
authors.lastname: Nance
authors.forename: Fadia
authors.initials: F
authors.lastname: Haddad
authors.forename: Dan M
authors.initials: DM
authors.lastname: Cooper
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Adams
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001772:Blood Cell Count; D016207:Cytokines / Q000097:blood; D017931:DNA Primers / Q000235:genetics; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D006352:Heart Ventricles / Q000254:growth & development*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D018482:Muscle, Skeletal / Q000254:growth & development*; D009929:Organ Size / Q000502:physiology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines; D017931:DNA Primers; D012739:Gonadal Steroid Hormones; D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs; D012333:RNA, Messenger