MicroRNA expression profile in intrauterine hypoxia-induced pulmonary hypoplasia in rats

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.

Gestational Hypoxia and Developmental Plasticity

“…The largest changes in miR that were found in the Huo study during fetal hypoxia were not in the expression of what are considered normal hypoxia-related miR. Instead, there was upregulation of miR-465 (~25-fold), and miR-377 (~20-fold), while miR-210 that is classically upregulated by hypoxia was only modestly increased by hypoxia (405). miR-327 was downregulated nearly 10-fold, while miR-338 was depressed~5 fold.…”

“…The adaptations in miR expression and function with regards to hypoxia are a developing area of research, and there is still much to understand about miR in the neonatal vasculature. There are only a few studies that have examined changes in miR in hypoxic fetal or neonatal lungs (324,353,405,1101,1115). The most comprehensive gestational hypoxia study to date that has examined miR in the lung is that of Huo et al in 2014 (405).…”

Excessive activation of NMDA receptor inhibits the protective effect of endogenous bone marrow mesenchymal stem cells on promoting alveolarization in bronchopulmonary dysplasia

“…However, the mechanism underlying the effects of intrauterine hypoxia on lung development is still unclear. We (17,22) previously reported that intrauterine hypoxia can induce alveolar dysplasia in the fetus and after birth.…”

The newborn sheep translational model for pulmonary arterial hypertension of the neonate at high altitude

“…The two most upregulated miRNAs were miR-465 and miR-377, while the most downregulated were miR-327 and miR-338. 140 Nothing is known about these miRNAs in lung development; however, miR-338 has been found to be downregulated in pulmonary fibrosis. 141 Xu et al reported a model of hypoxia-induced PPHN in rats with an increase in miR-126a-5p levels, which is involved in endothelial-to-mesenchymal transition and is likely acting through the p85-β/p-AKT (Protein kinase B) pathway.…”