Abstract
Preterm infants often experience hyperoxia while receiving supplemental oxygen. Prolonged exposure to hyperoxia during development is associated with pathologies such as bronchopulmonary dysplasia and retinopathy of prematurity. Over the last 25 years, however, experiments with animal models have revealed that moderate exposures to hyperoxia (e.g., 30-60% O(2) for days to weeks) can also have profound effects on the developing respiratory control system that may lead to hypoventilation and diminished responses to acute hypoxia. This plasticity, which is generally inducible only during critical periods of development, has a complex time course that includes both transient and permanent respiratory deficits. Although the molecular mechanisms of hyperoxia-induced plasticity are only beginning to be elucidated, it is clear that many of the respiratory effects are linked to abnormal morphological and functional development of the carotid body, the principal site of arterial O(2) chemoreception for respiratory control. Specifically, developmental hyperoxia reduces carotid body size, decreases the number of chemoafferent neurons, and (at least transiently) diminishes the O(2) sensitivity of individual carotid body glomus cells. Recent evidence suggests that hyperoxia may also directly or indirectly impact development of the central neural control of breathing. Collectively, these findings emphasize the vulnerability of the developing respiratory control system to environmental perturbations.