Effects of tracheal occlusion with retinoic acid administration on normal lung development.
BACKGROUND
Tracheal occlusion (TO) is an investigational therapy for severe congenital diaphragmatic hernia that decreases pulmonary hypoplasia, but sustained TO also induces deficient surfactant synthesis. Intramuscular maternal administration of retinoic acid (RA) in a surgical rabbit model of congenital diaphragmatic hernia showed a beneficial effect on lung maturation. We evaluated the potential of RA delivery into the trachea and studied the combined effects of TO and RA on normal lung development.


METHODS
Experiments were performed on normal rabbit fetuses. Liposomes and capric triglyceride (Miglyol®), alone and with RA, were administered in the trachea just before TO (d26). Lung morphology and surfactant production were studied at term (d30).


RESULTS
Tracheal occlusion increased lung weight and enhanced alveolar development but increased apoptotic activity and decreased surfactant expression. Tracheal injection of RA improved surfactant production to levels of normal controls.


CONCLUSIONS
We established the potential of liposome and Miglyol as RA vehicle for delivering this bioactive molecule in the fetal airways. Tracheal RA injection seems to oppose the effects of TO in fetuses with normal lungs. © 2017 John Wiley & Sons, Ltd.
EA7281 - Retinoids, Reproduction Developmental Diseases, Auvergne University, Clermont-Ferrand, France.|Fetal Maternal Medicine Unit, Obstetrics and Gynecology Department, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.
Amélie
http://orcid.org/0000-0001-6871-9044
A
Delabaere
EA7281 - Retinoids, Reproduction Developmental Diseases, Auvergne University, Clermont-Ferrand, France.|Biochemistry and Molecular Biology Department, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.
Geoffroy
G
Marceau
EA7281 - Retinoids, Reproduction Developmental Diseases, Auvergne University, Clermont-Ferrand, France.|Department of Paediatrics, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.
Karen
K
Coste
EA7281 - Retinoids, Reproduction Developmental Diseases, Auvergne University, Clermont-Ferrand, France.
Loïc
L
Blanchon
Department of Pathology, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.
Pierre-Jean
PJ
Déchelotte
EA7281 - Retinoids, Reproduction Developmental Diseases, Auvergne University, Clermont-Ferrand, France.
Pierre
P
Blanc
EA7281 - Retinoids, Reproduction Developmental Diseases, Auvergne University, Clermont-Ferrand, France.|Biochemistry and Molecular Biology Department, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.
Vincent
V
Sapin
EA7281 - Retinoids, Reproduction Developmental Diseases, Auvergne University, Clermont-Ferrand, France.|Fetal Maternal Medicine Unit, Obstetrics and Gynecology Department, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.
Denis
D
Gallot
D000402:Airway Obstruction / Q000196:embryology / Q000473:pathology; D000818:Animals; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000378:metabolism; D011817:Rabbits; D014132:Trachea / Q000473:pathology*; D014212:Tretinoin / Q000494:pharmacology*
D011663:Pulmonary Surfactants; D014212:Tretinoin