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Effects of maternal retinoic acid administration in a congenital diaphragmatic hernia rabbit model
Author(s) -
Gallot Denis,
Coste Karen,
Jani Jacques,
Roubliova Xenia,
Marceau Geoffroy,
Velemir Luka,
Verheyen An,
Lemery Didier,
Sapin Vincent,
Deprest Jan
Publication year - 2008
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/ppul.20829
Subject(s) - congenital diaphragmatic hernia , nitrofen , retinoid , medicine , retinoic acid , lung , fetus , pulmonary surfactant , tretinoin , endocrinology , respiratory system , diaphragmatic hernia , andrology , hernia , surgery , biology , biochemistry , pregnancy , genetics , gene
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. Pediatr Pulmonol. 2008; 43:594–603. © 2008 Wiley‐Liss, Inc.