Abstract
Congenital diaphragmatic hernia (CDH) is a devastating disease that still carries
a high mortality and morbidity rate. Poor outcomes for fetuses and infants with CDH
are mainly related to pulmonary hypoplasia (PH) and pulmonary vascular remodeling
that leads to pulmonary hypertension (PHTN). Over the last five decades, research
efforts have focused on modeling CDH not only to study the pathophysiology of the
diaphragmatic defect, pulmonary hypoplasia, and pulmonary hypertension, but also to
identify therapies that would promote lung growth and maturation, and correct vascular
remodeling. As CDH is a multifactorial condition whose etiology remains unknown, there
is not a single model of CDH, rather several ones that replicate different aspects
of this disease. While small animals like the mouse and the rat have mainly been used
to uncover biological pathways underlying the diaphragmatic defect and poor lung growth,
larger animals like the lamb and the rabbit models have been instrumental for pursuing
medical and surgical interventions. Overall, the use of animal models has indeed advanced
our knowledge on CDH and helped us test innovative therapeutic options. For example,
the lamb model of CDH has been the paradigm for testing fetal surgical procedures,
including tracheal occlusion, which has been translated to clinical use. In this review,
we outline the induction protocols of CDH in animals with the use of chemicals, dietary
changes, genetic alterations, and surgical maneuvers, and we describe the studies
that have translated experimental results to the bedside.
Keywords
congenital diaphragmatic hernia - pulmonary hypoplasia - lung development - fetal
surgery - FETO
