Abstract
Hypoxia is necessary for fetal development; however, excess hypoxia is detrimental. The mechanisms underlying the effects of hypoxia on lung development remain unclear, although important roles of microRNAs (miRNAs) during lung development have recently been established. However, the effect on lung development at an miRNA expression level, following changes in oxygen tension, have not yet been studied. In the present study, pregnant rats were exposed to a fraction of inspired oxygen of 10.5 or 21% for two days on gestation day 19, following which the body weight, lung wet weight, radial alveolar count (RAC) and mean linear intercept (Lm) of the newborn pups were analyzed on postnatal day 1. To define the role of miRNAs during lung development following intrauterine hypoxia exposure, the miRNA expression pattern was profiled using a miRNA microarray. The newborn rats in the hypoxic group exhibited statistically significant decreases in body weight, lung weight and the RAC, as well as a marked increase in the Lm. A total of 69 miRNAs were identified to have significant changes in expression, including 55 upregulated and 14 downregulated miRNAs. Quantitative polymerase chain reaction was used to validate the microarray results of six selected miRNAs. Therefore, the results indicated that late gestation intrauterine hypoxia exposure may cause lung injury and miRNAs may play important roles in this process.
Highlights
IntroductionExposure to environmental risk factors, Key words: hypoxia, lung development, pulmonary hypoplasia, microRNA, microarray including hypoxia, prenatal viral infections, drugs, smoking and stress, results in hypoxia and hypoxic lesions prenatally in ~80% and perinatally in 10‐20% of cases [1]
Environmental factors have an important role during embryonic development
Newborn rats at postnatal day 1 (P1) that had been exposed to intrauterine hypoxia from embryonic day 19 (E19) to E20 exhibited a significant body and lung wet weight reduction
Summary
Exposure to environmental risk factors, Key words: hypoxia, lung development, pulmonary hypoplasia, microRNA, microarray including hypoxia, prenatal viral infections, drugs, smoking and stress, results in hypoxia and hypoxic lesions prenatally in ~80% and perinatally in 10‐20% of cases [1]. These early environmental risk factors may affect the structural and/or functional development of the fetus and neonate. MicroRNAs (miRNAs) have been demonstrated to regulate a number of crucial developmental processes in a variety of organs, with an important role during lung morphogenesis recently established [5]. In order to create an equivalent rat model, hypoxia was initiated in the rats on embryonic day 19 (E19) in the present study
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