title: Effects of maternal retinoic acid administration in a congenital diaphragmatic hernia rabbit model.
abstract: Maternal retinoid administration has beneficial effects on lung development in the nitrofen rodent toxic model of congenital diaphragmatic hernia (DH). We wanted to investigate the effects in a surgical model, where the retinoid signaling pathway is not primarily disrupted by the toxic agent. We created DH in fetal rabbits at day 23 of gestation, administrated to the does all trans-retinoic acid (ATRA) or vehicle (VHC) intramuscularly for 8 consecutive days and harvested normal and operated (DH) fetuses at 31 d (n = 7 in each group). Normal lungs exposed to ATRA had increased surfactant protein mRNA levels without change in type II pneumocyte density. There was no measurable effect on lung-to-body weight ratio and airway morphometry by ATRA. In DH lungs (DH/VHC) surfactant protein mRNA levels were increased, as well as the density of type II pneumocytes. When supplemented with ATRA (DH/ATRA) these parameters returned to normal (VHC). Cell proliferation or apoptosis were not influenced by ATRA supplementation. In conclusion, maternal ATRA supplementation does not affect gross anatomic, morphologic or proliferation indices in hypoplastic lungs related to surgically induced DH in rabbit. However, ATRA lowers surfactant protein expression and normalizes type I/II pneumocyte ratio to what is observed in normal lungs.
authors.affiliation: Université d'Auvergne, JE2447 ARDEMO, F-63000, Clermont-Ferrand, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Gallot
authors.forename: Karen
authors.initials: K
authors.lastname: Coste
authors.forename: Jacques
authors.initials: J
authors.lastname: Jani
authors.forename: Xenia
authors.initials: X
authors.lastname: Roubliova
authors.forename: Geoffroy
authors.initials: G
authors.lastname: Marceau
authors.forename: Luka
authors.initials: L
authors.lastname: Velemir
authors.forename: An
authors.initials: A
authors.lastname: Verheyen
authors.forename: Didier
authors.initials: D
authors.lastname: Lemery
authors.forename: Vincent
authors.initials: V
authors.lastname: Sapin
authors.forename: Jan
authors.initials: J
authors.lastname: Deprest
mesh_terms: D000818:Animals; D015153:Blotting, Western; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects*; D005333:Fetus / Q000378:metabolism*; D006548:Hernia, Diaphragmatic / Q000378:metabolism; D065630:Hernias, Diaphragmatic, Congenital; D008168:Lung / Q000187:drug effects / Q000196:embryology / Q000503:physiopathology; D023421:Models, Animal; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics / Q000378:metabolism; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D051242:Caveolin 1; D018809:Proliferating Cell Nuclear Antigen; D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D014815:Vitamins; D014212:Tretinoin