title: Antenatal retinoic acid administration increases trophoblastic retinol-binding protein dependent retinol transport in the nitrofen model of congenital diaphragmatic hernia.
abstract: BACKGROUND
  Low pulmonary retinol levels and disrupted retinoid signaling pathway (RSP) have been implicated in the pathogenesis of congenital diaphragmatic hernia (CDH) and associated pulmonary hypoplasia (PH). It has been demonstrated that nitrofen disturbs the main retinol-binding protein (RBP)-dependent trophoblastic retinol transport. Several studies have demonstrated that prenatal treatment with retinoic acid (RA) can reverse PH in the nitrofen-induced CDH model. We hypothesized that maternal administration of RA can increase trophoblastic RBP-dependent retinol transport in a nitrofen model of CDH.
  
  
  METHODS
  Pregnant rats were treated with nitrofen or vehicle on gestational day 9 (D9) and sacrificed on D21. RA was given i.p. on D18, D19, and D20. Retinol and RA levels were measured using high-performance liquid chromatography. Immunohistochemistry was performed to evaluate trophoblastic expression of RBP. Expression levels of the primary RSP genes were determined using quantitative real-time PCR and immunohistochemistry.
  
  
  RESULTS
  Markedly increased trophoblastic RBP immunoreactivity was observed in CDH+RA compared to CDH. Significantly increased serum and pulmonary retinol and RA levels were detected in CDH+RA compared to CDH. Pulmonary expression of RSP genes and proteins were increased in CDH+RA compared to CDH.
  
  
  CONCLUSIONS
  Increased trophoblastic RBP expression and retinol transport after antenatal administration of RA suggest that retinol-triggered RSP activation may attenuate CDH-associated PH by elevating serum and pulmonary retinol levels.
authors.affiliation: Our Lady's Children's Hospital, National Children's Research Centre, Dublin, Ireland.
authors.forename: Balazs
authors.initials: B
authors.lastname: Kutasy
authors.affiliation: Our Lady's Children's Hospital, National Children's Research Centre, Dublin, Ireland.
authors.forename: Florian
authors.initials: F
authors.lastname: Friedmacher
authors.affiliation: Centre for Synthesis and Chemical Biology, School of Chemistry and Chemical Biology, University College Dublin, Dublin, Ireland.
authors.forename: Lara
authors.initials: L
authors.lastname: Pes
authors.affiliation: Our Lady's Children's Hospital, National Children's Research Centre, Dublin, Ireland.
authors.forename: David
authors.initials: D
authors.lastname: Coyle
authors.affiliation: Our Lady's Children's Hospital, National Children's Research Centre, Dublin, Ireland.
authors.forename: Takashi
authors.initials: T
authors.lastname: Doi
authors.affiliation: Centre for Synthesis and Chemical Biology, School of Chemistry and Chemical Biology, University College Dublin, Dublin, Ireland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Paradisi
authors.affiliation: Our Lady's Children's Hospital, National Children's Research Centre, Dublin, Ireland.
authors.forename: Prem
authors.initials: P
authors.lastname: Puri
mesh_terms: D000818:Animals; D001692:Biological Transport; D004195:Disease Models, Animal; D005260:Female; D020567:Fetal Weight; D065630:Hernias, Diaphragmatic, Congenital / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D010647:Phenyl Ethers / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D012177:Retinol-Binding Proteins / Q000378:metabolism*; D014212:Tretinoin / Q000633:toxicity*; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism*
chemical_list: D010647:Phenyl Ethers; D012177:Retinol-Binding Proteins; D014801:Vitamin A; D014212:Tretinoin; C007350:nitrofen