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Fetal Echocardiography and Pulsed-wave Doppler Ultrasound in a Rabbit Model of Intrauterine Growth Restriction
Published on: June 29, 2013
Lung microRNA deregulation associated with impaired alveolarization in rats after intrauterine growth restriction
Pauline Dravet-Gounot1,2,3,4,5, Cécile Morin1,2,3,5, Sébastien Jacques1,2,3
1Inserm, U1016, Institut Cochin, Paris, France.
Insights
Intrauterine growth restriction (IUGR) impairs lung development in preterm infants. This study reveals specific microRNAs (miRNAs) are altered in IUGR, affecting lung repair and communication, offering insights into bronchopulmonary dysplasia.
Area of Science:
- Respiratory Medicine
- Developmental Biology
- Molecular Biology
Background:
- Intrauterine growth restriction (IUGR) is a risk factor for bronchopulmonary dysplasia (BPD), a major complication of preterm birth.
- Previous studies demonstrated impaired lung alveolarization in IUGR rat models.
- Genome-wide analysis suggested involvement of cell adhesion pathways in IUGR-induced lung changes.
Purpose of the Study:
- To investigate microRNA (miRNA) expression profiles in the lungs of IUGR rat pups.
- To identify specific miRNAs and their target genes involved in lung alveolarization disorders caused by IUGR.
- To elucidate the mechanistic contribution of IUGR to impaired lung development.
Main Methods:
- Unbiased microRNA (miRNA) profiling using microarray assays in rat pups.
- Quantitative real-time PCR (qPCR) for miRNA validation at postnatal days 10 and 21.
- Bioinformatic analysis to predict target genes and associated pathways.
Main Results:
- Identified 13 differentially expressed miRNAs ( > 2-fold change) in IUGR versus control lungs.
- miRNA targets were associated with "tissue repair" at P10 and "cellular communication regulation" at P21.
- Found increased mRNA and protein levels of E2F3, a cell cycle regulator, in IUGR lungs at P21.
Conclusions:
- IUGR significantly alters miRNA expression during lung alveolarization.
- Specific miRNAs and their targets play a role in IUGR-related lung development impairment.
- Findings provide a foundation for understanding IUGR's role in bronchopulmonary dysplasia.
Abstract:
Intrauterine growth restriction (IUGR) was recently described as an independent risk factor of bronchopulmonary dysplasia, the main respiratory sequelae of preterm birth. We previously showed impaired alveolarization in rat pups born with IUGR induced by a low-protein diet (LPD) during gestation. We conducted a genome-wide analysis of gene expression and found the involvement of several pathways such as cell adhesion. Here, we describe our unbiased microRNA (miRNA) profiling by microarray assay and validation by qPCR at postnatal days 10 and 21 (P10 and P21) in lungs of rat pups with LPD-induced lung-alveolarization disorder after IUGR. We identified 13 miRNAs with more than two-fold differential expression between control lungs and LPD-induced IUGR lungs. Validated and predicted target genes of these miRNAs were related to "tissue repair" at P10 and "cellular communication regulation" at P21. We predicted the deregulation of several genes associated with these pathways. Especially, E2F3, a transcription factor involved in cell cycle control, was expressed in developing alveoli, and its mRNA and protein levels were significantly increased at P21 after IUGR. Hence, IUGR affects the expression of selected miRNAs during lung alveolarization. These results provide a basis for deciphering the mechanistic contributions of IUGR to impaired alveolarization.
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