171 - Perinatal Selenium Deficiency Decreases Survival and Worsens Alveolarization Deficits in Hyperoxia-exposed Newborn Mice

Poster Number: 171
Publication Number: 171.438

Lora C. Bailey-Downs, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Laura Sherlock, University of Colorado School of Medicine, Aurora, CO, United States; Michaela N. Crossley, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Paul T. Pierce, University of Oklahoma College of Medicine, Oklahoma City, OK, United States; Shirley Wang, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Lynette KK.. Rogers, Ohio State University/Nationwide Children's Hospital, Columbus, OH, United States; Peter F. Vitiello, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Trent Tipple, Oklahoma Childrens Hospital / University of Oklahoma College of Medicine, Oklahoma City, OK, United States

Background: Oxygen toxicity and antioxidant deficiencies contribute to the development of bronchopulmonary dysplasia (BPD) in prematurely born infants. Selenium (Se) is an essential modulator of endogenous antioxidant responses. Premature infants are Se deficient and Se deficiency is correlated with BPD development. Mechanisms by which Se contributes to neonatal lung development and endogenous antioxidant responses are unknown.

Objective: The presents studies were designed to test the hypothesis that perinatal Se deficiency modulates hyperoxic sensitivity in an experimental model of BPD.

Design/Methods: MMale and female C3H/HeN mice were fed Se-sufficient (SeS; 0.4 ppm Na2SeO3) or Se-deficient (SeD; < 0.01 ppm Na2SeO3) diets from weaning and subsequently bred to create SeS and SeD litters. SeS and SeD pups were exposed to room air (21% O2) or hyperoxia (85% O2) from birth through 14 d. SeS and SeD pups were nursed by dams of corresponding diets. Dams were rotated between 21% and 85% O2 every 24 h to prevent O2 toxicity. Upon sacrifice, lungs were inflated, H&E stained, and analyzed for alveolar size (micron2) and number (normalized to total surface area). Data (mean±SD, n=17-29) were analyzed by 2-way ANOVA followed by Tukey’s post-hoc (p< 0.0001).

Results: Hyperoxia-exposed SeD pups exhibited 44% mortality (17/39) compared with 4% mortality in hyperoxia-exposed SeS mice (1/25). Analyses indicated independent effects of diet and exposure on alveolar size and number. Specifically, SeD pups born to and nursed by SeD dams exhibited baseline deficits in alveolarization characterized by increased alveolar size (50.5±6.4 vs 43.8±3.7) and decreased alveolar number (223±38 vs 270±27). Alveolar size and number were altered by hyperoxia in SeS pups (54.6±4.5 and 183±24), respectively. Hyperoxia-exposed SeD pups exhibited the most dramatic deficits in alveolar size (67±6.4) and number (134±19).

Conclusion(s): Consistent with our hypothesis, our data suggest that Se modulates perinatal lung development and alters responses to hyperoxia in newborn mice. Comprehensive modeling of Se deficiency, a common clinical scenario in extremely preterm infants, will enhance the rigor with which we investigate strategies to enhanceendogenous antioxidant responses, promote optimal lung development, and prevent BPD.