title: Prenatal hypoxia downregulates the expression of pulmonary vascular endothelial growth factor and its receptors in fetal mice.
abstract: BACKGROUND
  Previous reports showed that prenatal hypoxia delays the process of lung maturation. Vascular endothelial growth factor (VEGF) and its receptors were important for lung development. However, the role of VEGF and VEGF receptors in altered fetal lung development and maturation induced by prenatal hypoxia remains unknown.
  
  
  OBJECTIVE
  To elucidate the role of VEGF and VEGF receptors in altered fetal lung development and maturation induced by prenatal hypoxia.
  
  
  METHODS
  Lung sections of control and maternal hypoxic fetal mice were used for the determination of lung development and total RNA isolated from lung homogenates were used for determination of the expression patterns of VEGF, Flt-1, Flk-1, hypoxia-inducible factor (HIF)-1α, HIF-2α, surfactant protein (SP)-A, SP-B, SP-C, and SP-D by quantitative real-time RT-PCR.
  
  
  RESULTS
  Prenatal hypoxia resulted in fetal mice body weight gain impairment, delayed fetal pulmonary aeration and maturation. Pulmonary SP-A, SP-B, SP-C, and SP-D mRNA were all decreased in the prenatal hypoxia group. In addition, we demonstrated that prenatal hypoxia inhibited the developmental increase of pulmonary HIF-1α and HIF-2α expression and resulted in decreasing VEGF and its receptors (Flt-1 and Flk-1) at the mRNA expression level and VEGF protein level in fetal lungs. These inhibitory effects persisted and progressed even when the dams were returned to air.
  
  
  CONCLUSIONS
  We suggest that prenatal hypoxia insults, at least in late gestation, influence pulmonary VEGF and VEGF receptor expression through the down-regulation of HIF pathways and impair fetal lung growth and maturation.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan, ROC. tsaopn@ntu.edu.tw
authors.forename: Po-Nien
authors.initials: PN
authors.lastname: Tsao
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Wei
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D005325:Fetal Organ Maturity; D020567:Fetal Weight; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D000860:Hypoxia / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000098:blood supply* / Q000196:embryology; D051379:Mice; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011651:Pulmonary Artery / Q000196:embryology / Q000378:metabolism*; D037661:Pulmonary Surfactant-Associated Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D037661:Pulmonary Surfactant-Associated Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099162:Endothelial PAS Domain-Containing Protein 1; C497443:Hif1a protein, mouse; C467480:vascular endothelial growth factor A, mouse; C501163:Flt1 protein, mouse