Page Banner

United States Department of Agriculture

Agricultural Research Service

Research Project: MOLECULAR, CELLULAR, AND REGULATORY ASPECTS OF NUTRITIONAL METABOLISM DURING CHILDHOOD DEVELOPMENT

Location: Children's Nutrition Research Center

Title: Exposure to hyperoxia in the neonatal period alters bone marrow function

Authors
item Kienstra, Kirsten -
item Gonzales, Naomi -
item Hirschi, Karen -

Submitted to: Pediatric Academic Society
Publication Type: Abstract Only
Publication Acceptance Date: February 17, 2009
Publication Date: May 2, 2009
Citation: Kienstra, K.A., Gonzales, N.M., Hirschi, K.K. 2009. Exposure to hyperoxia in the neonatal period alters bone marrow function [abstract]. Pediatric Academic Society. Abstract No. 5506.103.

Technical Abstract: Oxygen is often life saving in preterm infants, however, excessive exposure may lead to blood vessel and tissue injury in the lung and retina. Oxygen-treated neonates often exhibit bone marrow (BM) suppression requiring blood product transfusions. However, we do not know whether oxygen is directly toxic to BM. We established a neonatal mouse model to test the effects of hyperoxia on BM function. We found that following neonatal hyperoxia in recipient mouse pups, donor BM cells engrafted into the hematopoietic system at high levels. We hypothesized that neonatal hyperoxia induces cellular, and molecular alterations in hematopoietic stem cells (HSC), and cells within the BM niche that are needed to support HSC function. To test this hypothesis, we examined the impact of hyperoxia on the function of HSC and on HSC niche signaling pathways. Pups were placed in >95% oxygen for 1-5d, with room air littermates as controls. HSC were harvested at serial time-points and analyzed using methylcellulose culture, competitive transplantation, and cell cycle analysis. BM-resident HSC and vascular endothelial cells were analyzed by quantitative real time RT-PCR to assess for oxygen-induced alterations in HSC niche signaling pathways. Oxygen-exposed HSC cultured in methylcellulose trended toward fewer colony-forming units compared to room air controls, with significant differences after 5d. The effect of hyperoxia on competitive hematopoietic engraftment varied based on exposure time, with lower levels after 3 & 5d, and significantly higher levels after 1 & 4d. Oxygen-exposed BM stem/progenitors trended toward a higher fraction of cells in an active cycling phase, with significant differences after 3d. Furthermore, expression levels of several signaling factors in BM-resident HSC and vascular endothelial cells were altered following hyperoxia. Neonatal oxygen exposure diminished the proliferative and engraftment potential of HSC, with variations based on duration of hyperoxia. Neonatal hyperoxia increased the fraction of actively cycling and differentiating cells, which may deplete the quiescent HSC population. Hyperoxia altered signaling pathways known to be important in HSC niche regulation. The impact of hyperoxia on neonatal BM likely involves multiple mechanisms, including direct hematopoietic cell injury and disruption of the BM niche. Ongoing studies will elucidate the molecular mechanisms mediating the hyperoxia-induced BM alterations.

Last Modified: 10/1/2014
Footer Content Back to Top of Page