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Updated: May 5, 2026
Fetal Echocardiography and Pulsed-wave Doppler Ultrasound in a Rabbit Model of Intrauterine Growth Restriction
Published on: June 29, 2013
Effect of two models of intrauterine growth restriction on alveolarization in rat lungs: morphometric and gene
Elodie Zana-Taieb1, Laura Butruille, Marie-Laure Franco-Montoya
1Institut National de la Santé Et de la Recherche Médicale (INSERM) U767, Paris, France ; PremUp, Paris, France ; Service de Médecine et Réanimation néonatales de Port-Royal, Groupe hospitalier Cochin, Broca, Hôtel-Dieu, Assistance Publique - Hôpitaux de Paris, Paris, France ; Université Paris Descartes, Paris, France.
Insights
Maternal protein deprivation causes lasting lung alveolarization defects in IUGR rat pups, unlike nitric oxide synthase inhibition which causes temporary impairment. This suggests programming alterations in lung development.
Area of Science:
- Neonatal Physiology
- Pulmonary Development
- Developmental Biology
Background:
- Intrauterine growth restriction (IUGR) in preterm infants is linked to bronchopulmonary dysplasia, a condition marked by impaired alveolarization.
- Understanding the mechanisms of IUGR-induced lung developmental deficits is crucial for improving preterm infant outcomes.
Purpose of the Study:
- To investigate the distinct impacts of two IUGR models (maternal protein deprivation and nitric oxide synthase inhibition) on postnatal lung alveolarization in rat pups.
- To identify specific molecular pathways affected by each IUGR model during critical lung development periods.
Main Methods:
- Utilized two rat models of IUGR: low protein diet (LPD) and Nω-nitro-L-arginine methyl ester (L-NAME) administration.
- Assessed lung morphometry (alveolar surface, mean linear intercept, radial alveolar count) at postnatal days 4, 21, and 30.
- Performed transcriptomic analysis focusing on genes involved in alveolarization.
Main Results:
- LPD-induced IUGR resulted in sustained decreases in alveolar surface and radial alveolar count, indicating arrested alveolarization at day 21.
- L-NAME-induced IUGR caused transient deficits in alveolarization at day 4, with complete recovery by day 21.
- Key alveolarization-related genes (VEGF, FGF, FGFR, MMP) were downregulated in the L-NAME model but not significantly altered in the LPD model.
Conclusions:
- Maternal protein deprivation leads to persistent impairment of lung alveolarization in IUGR rat pups.
- Nitric oxide synthase inhibition causes temporary lung development issues that are corrected postnatally.
- The distinct effects suggest different underlying mechanisms, with LPD-induced deficits potentially involving altered developmental programming rather than direct growth factor pathway disruption.
Abstract:
Intrauterine growth restriction (IUGR) in preterm infants increases the risk of bronchopulmonary dysplasia, characterized by arrested alveolarization. We evaluated the impact of two different rat models (nitric oxide synthase inhibition or protein deprivation) of IUGR on alveolarization, before, during, and at the end of this postnatal process. We studied IUGR rat pups of dams fed either a low protein (LPD) or a normal diet throughout gestation and pups of dams treated by continuous infusion of Nω-nitro-L-arginine methyl ester (L-NAME) or its diluent on the last four days of gestation. Morphometric parameters, alveolar surface (Svap), mean linear intercept (MLI) and radial alveolar count (RAC) and transcriptomic analysis were determined with special focus on genes involved in alveolarization. IUGR pups regained normal weight at day 21 in the two treated groups. In the LPD group, Svap, MLI and RAC were not different from those of controls at day 4, but were significantly decreased at day 21, indicating alveolarization arrest. In the L-NAME group, Svap and RAC were significantly decreased and MLI was increased at day 4 with complete correction at day 21. In the L-NAME model, several factors involved in alveolarization, VEGF, VEGF-R1 and -R2, MMP14, MMP16, FGFR3 and 4, FGF18 and 7, were significantly decreased at day 4 and/or day 10, while the various factors studied were not modified in the LPD group. These results demonstrate that only maternal protein deprivation leads to sustained impairment of alveolarization in rat pups, whereas L-NAME impairs lung development before alveolarization. Known growth factors involved in lung development do not seem to be involved in LPD-induced alveolarization disorders, raising the question of a possible programming of altered alveolarization.
