Retinoic acid and tracheal occlusion for diaphragmatic hernia treatment in rabbit fetuses

Prenat Diagn. 2018 Jun;38(7):482-492. doi: 10.1002/pd.5256.


Introduction: Lung hypoplasia and pulmonary arterial hypertension in congenital diaphragmatic hernia lead to a high perinatal mortality. Although sustained fetoscopic tracheal occlusion (TO) improves lung development, a major side effect is abnormal pneumocyte differentiation. This study evaluated the potential ability of intratracheal retinoic acid (RA) administration to reduce adverse effects of sustained TO in a rabbit model of diaphragmatic hernia.

Methods: A left diaphragmatic defect was created on day 23 in time-dated pregnant rabbits. On day 28, the same rabbits underwent sham surgery or TO, with an injection of empty or RA-loaded liposomes. On day 30, the fetuses were harvested, and the lungs were processed for histology, immunohistochemistry, and gene expression quantification.

Results: A tracheal RA injection at the time of TO had no effect on the lung-to-body-weight ratio, radial alveolar count or lung connective tissue composition. Retinoic acid plus TO had synergic effects on vascular measurements, proportional medial thickness, and endothelin-1 receptor type-A gene expression. The most noticeable effect was recovery of normal pneumocyte differentiation.

Conclusion: Retinoic acid plus TO prevented abnormal pneumocyte differentiation and seemed to have a beneficial effect on pulmonary vascularization.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Apoptosis / drug effects
  • Collagen / metabolism
  • Elastin / metabolism
  • Female
  • Fetal Diseases / surgery*
  • Fetoscopy
  • Hernia, Diaphragmatic / therapy*
  • Lung / drug effects*
  • Lung / embryology
  • Lung / metabolism
  • Pregnancy
  • Pulmonary Surfactants / metabolism
  • Rabbits
  • Trachea / surgery*
  • Tretinoin / administration & dosage*


  • Antineoplastic Agents
  • Pulmonary Surfactants
  • Tretinoin
  • Collagen
  • Elastin