Children who were born prematurely and exposed to hyperoxia are more likely to have reduced lung function and increased blood pressure compared to children who were born at normal gestation and exposed to room air.
Adult mice exposed to hyperoxia as newborns have fewer Type II cells (green)
than siblings exposed to room air.
Consistent with these epidemiologic findings, adult mice exposed to hyperoxia as newborns have reduced lung function attributed in part to altered development of alveolar epithelial type I and type II cells. Type II cells produce pulmonary surfactant lipids and proteins that maintain alveolar homeostasis and immunity against respiratory pathogens. They are also progenitors for type I cells that exchange oxidant gases between the lung and blood. Not only do these cellular changes persist, but significant vascular pruning and pulmonary hypertension occurs as mice age.
These findings suggest neonatal oxygen has reprogrammed epithelial and vascular progenitor cells required for normal lung development and its maintenance over a life span. By understanding how neonatal oxygen reprograms epithelial and vascular progenitor cells, we hope to gain insight into how it adversely affects lung function of children born prematurely.
Yee M, White RJ, Awad HA, Bates WA, McGrath-Morrow SA, and O’Reilly MA. Neonatal hyperoxia causes pulmonary vascular disease and shortens life-span in aging mice. Am. J. Pathol. 178: 2601 - 2610, 2011.
Yee M, Chess PR, McGrath-Morrow SA, Wang Z, Gelein R, Zhou R, Dean DA, Notter RH, and O'Reilly MA. Neonatal oxygen adversely affects lung function in adult mice without altering surfactant composition or activity. Am J Physiol Lung Cell Mol Physiol 297: L641-649 2009.
Yee M, Vitiello PF, Roper JM, Staversky RJ, Wright TW, McGrath-Morrow SA, Maniscalco W, Finkelstein JN, and O'Reilly MA. Type II epithelial cells are a critical target for hyperoxia-mediated impairment of postnatal lung development. Am J Physiol Lung Cell Mol Physiol 291: L1101-1111, 2006.