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.
展开▼
机译：极早产儿通常接受超生理氧疗，这会导致支气管肺发育不良 （BPD） 的发展。这些婴儿表现出抗氧化能力受损，部分原因是硒 （Se） 缺乏。Se 对于基础和诱导性抗氧化反应至关重要。本研究利用围产期 Se 缺乏 （SeD） 小鼠模型来确定新生儿高氧暴露和 SeD 对肺泡形成和抗氧化反应的综合影响，包括确定受影响的发育途径。生成 Se-sufficient （SeS） 和 SeD C3H/HeN 繁殖对，幼仔从出生到 14 天暴露在室内空气或 85% O 2 中。进行生存、抗氧化蛋白表达和 RNA seq 分析。在高氧暴露的 SeD 幼崽中观察到超过 40% 的死亡率。存活的 SeD 幼仔比高氧暴露的 SeS 幼仔具有更大的肺生长缺陷。SeD 幼仔的 Gpx2 和 4 蛋白和 Gpx 活性显著降低。Nrf2 调节蛋白 Nqo1 和 Gclc 在暴露于高氧的 SeD 幼仔中增加。RNA seq 显示 Wnt/β-catenin 和 Notch 通路显著降低。Se 是围产期肺发育和抗氧化反应的生物学相关调节剂，尤其是在高氧暴露的情况下。RNA seq 分析表明，硒缺乏症对正常肺发育至关重要的途径失调。
展开▼
