title: Increased uptake of dietary retinoids at the maternal-fetal barrier in the nitrofen model of congenital diaphragmatic hernia.
abstract: OBJECTIVE
  The retinol signaling pathway is disrupted in congenital diaphragmatic hernia (CDH). Since there is no fetal retinol synthesis, maternal retinol has to cross the placenta. Nitrofen interferes with the retinol-binding protein (RBP) transfer pathway in CDH. However, in RBP knockout mice, retinol has been shown to be present. In this model, increased uptake of maternal dietary retinyl ester (RE) bounded in low-dense-lipoprotein (LDL) through low-density-lipoprotein-receptor 1 (LRP1) and increased activity of RE hydrolysis by lipoprotein-lipase (LPL) have been found. The aim of this study was to investigate the RE transfer pathway in the nitrofen CDH model.
  
  
  METHODS
  Pregnant rats were treated with nitrofen or vehicle on gestational day (D9) and sacrificed on D21. Immunohistochemistry was performed to evaluate LRP1 and LPL protein expression. Serum LDL levels were measured by ELISA. Pulmonary and serum retinoid levels were measured using HPLC.
  
  
  RESULTS
  Markedly increased trophoblastic and pulmonary LRP1 and LPL immunoreactivity were observed in CDH compared to controls. Significantly increased serum LDL and RE levels were observed in CDH compared to controls.
  
  
  CONCLUSIONS
  The increased uptake of dietary retinoids at the maternal-fetal barrier in the nitrofen CDH model suggests that the RE transfer pathway may be the main source of retinol in this model.
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Balazs
authors.initials: B
authors.lastname: Kutasy
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Florian
authors.initials: F
authors.lastname: Friedmacher
authors.affiliation: Centre for Synthesis and Chemical Biology, School of Chemistry & Chemical Biology, University College Dublin, Dublin, Ireland.
authors.forename: Lara
authors.initials: L
authors.lastname: Pes
authors.affiliation: Centre for Synthesis and Chemical Biology, School of Chemistry & Chemical Biology, University College Dublin, Dublin, Ireland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Paradisi
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland. Electronic address: prem.puri@ncrc.ie.
authors.forename: Prem
authors.initials: P
authors.lastname: Puri
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D065630:Hernias, Diaphragmatic, Congenital / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007150:Immunohistochemistry; D008077:Lipoproteins, LDL / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D010647:Phenyl Ethers / Q000633:toxicity; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012176:Retinoids / Q000494:pharmacology*
chemical_list: D008077:Lipoproteins, LDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010647:Phenyl Ethers; D012176:Retinoids; C007350:nitrofen
keywords: Congenital diaphragmatic hernia; Dietary retinoids; Nitrofen; Placenta; Retinol