Congenital diaphragmatic hernia: a retinoid-signaling pathway disruption during lung development?
Congenital diaphragmatic hernia (CDH) usually occurs sporadically. The prognosis remains poor, with a 50% perinatal mortality rate. Most deaths result from hypoxemia due to lung hypoplasia and abnormal development of pulmonary vasculature that results in persistent pulmonary hypertension. Our current understanding of the pathogenesis of CDH is based on an assumption linking herniation of abdominal viscera into the thorax with compression of the developing lung. Pulmonary hypoplasia, however, can also result from reduced distension of the developing lung secondary to impaired fetal breathing movements. Moreover, a nitrofen-induced CDH model shows that lung hypoplasia precedes the diaphragmatic defect, leading to a "dual-hit hypothesis." Recent data reveal the role of a retinoid-signaling pathway disruption in the pathogenesis of CDH. We describe the clinical and epidemiological aspects of human CDH, the metabolic and molecular aspects of the retinoid-signaling pathway, and the implications of retinoids in the development of the diaphragm and the lung. Finally, we highlight the existing links between CDH and disruption of the retinoid-signaling pathway, which may suggest an eventual use of retinoids in the treatment of CDH.
Maternal Fetal Medicine Unit, Maternité Hôtel-Dieu, Centre Hospitalier Universitaire, Clermont-Ferrand, France.
Denis
D
Gallot
Geoffroy
G
Marceau
Karen
K
Coste
Hélène
H
Hadden
Elisabeth
E
Robert-Gnansia
Hélène
H
Laurichesse
Pierre J
PJ
Déchelotte
André
A
Labbé
Bernard
B
Dastugue
Didier
D
Lémery
Vincent
V
Sapin
D000818:Animals; D003964:Diaphragm / Q000002:abnormalities / Q000196:embryology / Q000473:pathology; D005260:Female; D005315:Fetal Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006548:Hernia, Diaphragmatic / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D006976:Hypertension, Pulmonary / Q000151:congenital / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008168:Lung / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D015619:Respiratory System Abnormalities / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D012176:Retinoids / Q000378:metabolism* / Q000627:therapeutic use; D015398:Signal Transduction
D012176:Retinoids