Related Experiment Video
Updated: Apr 21, 2026
A Rat Model of Mild Intrauterine Hypoperfusion with Microcoil Stenosis
Published on: January 7, 2018
Impaired alveolarization and intra-uterine growth restriction in rats: a postnatal genome-wide analysis
E Zana-Taieb1, H Pham, M L Franco-Montoya
1Université Paris Descartes, Paris, France; Fondation PremUp, 53 avenue de l'Observatoire, 75014 Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U1141, Paris, France; Assistance Publique - Hôpitaux de Paris, Service de Médecine et Réanimation Néonatales de Port-Royal, Groupe Hospitalier Cochin, Broca, Hôtel-Dieu, 53 Avenue de l'Observatoire, 75014 Paris, France.
Insights
Intra-uterine growth restriction (IUGR) impairs lung development in preterm infants. This study reveals that deregulation of the peroxisome proliferator-activated receptor (PPAR) pathway is a key mechanism contributing to impaired alveolarization in IUGR models.
Area of Science:
- Pulmonary Medicine
- Developmental Biology
- Genomics
Background:
- Intra-uterine growth restriction (IUGR) significantly elevates the risk of bronchopulmonary dysplasia in preterm infants, characterized by arrested alveolarization and abnormal angiogenesis.
- Previous rodent models of IUGR using a low protein diet (LPD) demonstrated impaired alveolarization but did not identify modifications in classical lung development factors.
Purpose of the Study:
- To investigate genome-wide transcriptomic changes in a rodent model of LPD-induced IUGR during key stages of lung alveolarization.
- To identify molecular pathways involved in impaired alveolarization associated with IUGR.
Main Methods:
- Genome-wide microarray analysis was performed on 120 rat pups with LPD-induced IUGR and controls at postnatal days 4, 10, and 21.
- Data analysis utilized Arraymining, DAVID, and KEGG software, with validation through qRT-PCR and Western blots.
- Functional classification identified significantly altered pathways, focusing on cell adhesion molecules, cardiac muscle contraction, and PPAR signaling.
Main Results:
- Significant numbers of transcripts were up- and down-regulated at all three time points, with the largest changes observed at P21.
- Functional analysis highlighted the peroxisome proliferator-activated receptor (PPAR) pathway as notably affected.
- Protein analysis confirmed PPAR pathway involvement, showing increased FABP4 (an activator) at P4 and increased adiponectin at P21.
Conclusions:
- Deregulation of the PPAR pathway is implicated as a significant factor in the impaired alveolarization observed in IUGR.
- These findings provide novel insights into the molecular mechanisms underlying IUGR-associated lung developmental defects.
- The study's comprehensive dataset is publicly available on the Gene Expression Omnibus (GEO) database (GEO Accession No. GSE56956).
Abstract:
Intra-uterine growth restriction (IUGR) dramatically increases the risk of bronchopulmonary dysplasia in preterm babies, a disease characterized by arrested alveolarization and abnormal microvascular angiogenesis. We have previously described a rodent low protein diet (LPD) model of IUGR inducing impaired alveolarization, but failed to demonstrate any modification of the classical factors involved in lung development. We performed a genome-wide microarray analysis in 120 rat pups with LPD-induced IUGR and their controls, at three key time points of the alveolarization process: postnatal day 4 (P4): start of alveolarization; P10: peak of the alveolarization process and P21: end of the alveolarization process. Results were analysed using Arraymining, DAVID and KEGG software and validated by qRT-PCR and western blots. Considering a cut-off of 2:1 as significant, 67 transcripts at P4, 102 transcripts at P10 and 451 transcripts at P21 were up-regulated, and 89 transcripts at P4, 25 transcripts at P10 and 585 transcripts at P21 were down-regulated. Automatic functional classification identified three main modified pathways, 'cell adhesion molecules', 'cardiac muscle contraction' and 'peroxisome proliferator-activated receptor' (PPAR). Protein analysis confirmed involvement of the PPAR pathway, with an increase of FABP4, an activator of this pathway, at P4 and an increase of adiponectin at P21. Other data also suggest involvement of the PPAR pathway in impaired alveolarization. Our results show that deregulation of the PPAR pathway may be an important component of the mechanism inducing impaired alveolarization observed in IUGR. The complete dataset is available as GEO profiles on the Gene Expression Omnibus (GEO) database ( www.ncbi.nih.gov/geo/, GEO Accession No. GSE56956).
More Related Videos
14:19Fetal Echocardiography and Pulsed-wave Doppler Ultrasound in a Rabbit Model of Intrauterine Growth Restriction
Published on: June 29, 2013
07:36Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
