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Published on: October 19, 2013
Selenium Deficiency Exacerbates Hyperoxia-Induced Lung Injury in Newborn C3H/HeN Mice
Lora C Bailey-Downs1, Laura G Sherlock2, Michaela N Crossley1
1University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Insights
Selenium deficiency exacerbates lung injury in preterm infants exposed to oxygen, increasing mortality and hindering lung development by disrupting key cellular pathways.
Area of Science:
- Neonatal Medicine
- Pulmonology
- Biochemistry
Background:
- Extremely preterm infants often receive supraphysiological oxygen, increasing risk for bronchopulmonary dysplasia (BPD).
- These infants have reduced antioxidant capacity, partly due to selenium (Se) deficiency, which is crucial for antioxidant defenses.
Purpose of the Study:
- To investigate the combined impact of perinatal selenium deficiency and newborn hyperoxia on lung development and antioxidant responses in a mouse model.
- To identify specific developmental pathways affected by selenium deficiency under hyperoxia.
Main Methods:
- A mouse model of perinatal selenium deficiency (SeD) and sufficiency (SeS) was used.
- Pups were exposed to 85% oxygen (hyperoxia) or room air from birth to 14 days.
- Evaluated survival, antioxidant protein expression (Gpx2, Gpx4, Nqo1, Gclc), and performed RNA sequencing.
Main Results:
- Hyperoxia-exposed SeD pups experienced over 40% mortality and significant lung growth deficits compared to SeS pups.
- SeD pups showed decreased Gpx2 and Gpx4 protein levels and Gpx activity.
- Hyperoxia-exposed SeD pups had increased Nrf2-regulated proteins (Nqo1, Gclc) but decreased Wnt/β-catenin and Notch pathway signaling.
Conclusions:
- Selenium is vital for perinatal lung development and antioxidant defense, particularly during hyperoxia exposure.
- Selenium deficiency dysregulates critical developmental pathways (Wnt/β-catenin, Notch), contributing to lung injury in preterm infants.
Abstract:
Extremely preterm infants are often treated with supraphysiological oxygen, which contributes to the development of bronchopulmonary dysplasia (BPD). These same infants exhibit compromised antioxidant capacities due in part to selenium (Se) deficiency. Se is essential for basal and inducible antioxidant responses. The present study utilized a perinatal Se deficiency (SeD) mouse model to identify the combined effects of newborn hyperoxia exposure and SeD on alveolarization and antioxidant responses, including the identification of affected developmental pathways. Se-sufficient (SeS) and SeD C3H/HeN breeding pairs were generated, and pups were exposed to room air or 85% O2 from birth to 14 d. Survival, antioxidant protein expression, and RNA seq analyses were performed. Greater than 40% mortality was observed in hyperoxia-exposed SeD pups. Surviving SeD pups had greater lung growth deficits than hyperoxia-exposed SeS pups. Gpx2 and 4 protein and Gpx activity were significantly decreased in SeD pups. Nrf2-regulated proteins, Nqo1 and Gclc were increased in SeD pups exposed to hyperoxia. RNA seq revealed significant decreases in the Wnt/β-catenin and Notch pathways. Se is a biologically relevant modulator of perinatal lung development and antioxidant responses, especially in the context of hyperoxia exposure. The RNA seq analyses suggest pathways essential for normal lung development are dysregulated by Se deficiency.
