Intrauterine Hypoxia and Epigenetic Programming in Lung Development and Disease

Clinically, intrauterine hypoxia is the foremost cause of perinatal morbidity and developmental plasticity in the fetus and newborn infant. Under hypoxia, deviations occur in the lung cell epigenome. Epigenetic mechanisms (e.g., DNA methylation, histone modification, and miRNA expression) control phenotypic programming and are associated with physiological responses and the risk of developmental disorders, such as bronchopulmonary dysplasia. This developmental disorder is the most frequent chronic pulmonary complication in preterm labor. The pathogenesis of this disease involves many factors, including aberrant oxygen conditions and mechanical ventilation-mediated lung injury, infection/inflammation, and epigenetic/genetic risk factors. This review is focused on various aspects related to intrauterine hypoxia and epigenetic programming in lung development and disease, summarizes our current knowledge of hypoxia-induced epigenetic programming and discusses potential therapeutic interventions for lung disease.