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Updated: May 10, 2026
Fetal Echocardiography and Pulsed-wave Doppler Ultrasound in a Rabbit Model of Intrauterine Growth Restriction
Published on: June 29, 2013
Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain
Erwin van Vliet1, Elisenda Eixarch, Miriam Illa
1Department of Maternal-Fetal Medicine, Institut Clinic de Ginecologia, Obstetricia i Neonatologia-ICGON, Hospital Clinic and Institut d'Investigacions Biomediques August Pi i Sunyer-IDIBAPS, University of Barcelona, Barcelona, Spain.
Insights
Intrauterine Growth Restriction (IUGR) causes significant fetal brain metabolic changes, impacting neurodevelopment. Researchers identified specific metabolites like asparagine and ornithine as potential biomarkers for early IUGR diagnosis.
Area of Science:
- Perinatal Medicine
- Neuroscience
- Metabolomics
Background:
- Intrauterine Growth Restriction (IUGR) affects 5-10% of pregnancies, posing a risk for abnormal neurodevelopment.
- Perinatal diagnosis of IUGR-related neurodevelopmental issues is challenging.
- Identifying fetal brain biochemical alterations is crucial for biomarker development.
Purpose of the Study:
- To investigate the mechanistic effects of IUGR on the fetal brain.
- To identify potential metabolite biomarkers for IUGR-related abnormal neurodevelopment.
Main Methods:
- A rabbit model of IUGR was created using uteroplacental vessel ligation.
- Fetal brains were analyzed using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS).
- Metabolomic profiles were compared between control and IUGR groups.
Main Results:
- IUGR fetuses exhibited significantly lower birth and brain weights.
- 18 out of 78 identified metabolites showed significant differences between control and IUGR brains.
- Metabolite alterations correlated with IUGR severity, indicating predictive potential.
Conclusions:
- IUGR induces metabolic disturbances in the fetal brain, affecting neuronal viability, energy, and amino acid metabolism.
- Asparagine, ornithine, N-acetylaspartylglutamic acid, N-acetylaspartate, and palmitoleic acid are identified as potential biomarkers.
- These metabolites may aid in the perinatal diagnosis of IUGR-related abnormal neurodevelopment.
Background:
Intrauterine Growth Restriction (IUGR) due to placental insufficiency occurs in 5-10% of pregnancies and is a major risk factor for abnormal neurodevelopment. The perinatal diagnosis of IUGR related abnormal neurodevelopment represents a major challenge in fetal medicine. The development of clinical biomarkers is considered a promising approach, but requires the identification of biochemical/molecular alterations by IUGR in the fetal brain. This targeted metabolomics study in a rabbit IUGR model aimed to obtain mechanistic insight into the effects of IUGR on the fetal brain and identify metabolite candidates for biomarker development.
Methodology/Principal Findings:
At gestation day 25, IUGR was induced in two New Zealand rabbits by 40-50% uteroplacental vessel ligation in one horn and the contralateral horn was used as control. At day 30, fetuses were delivered by Cesarian section, weighed and brains collected for metabolomics analysis. Results showed that IUGR fetuses had a significantly lower birth and brain weight compared to controls. Metabolomics analysis using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and database matching identified 78 metabolites. Comparison of metabolite intensities using a t-test demonstrated that 18 metabolites were significantly different between control and IUGR brain tissue, including neurotransmitters/peptides, amino acids, fatty acids, energy metabolism intermediates and oxidative stress metabolites. Principle component and hierarchical cluster analysis showed cluster formations that clearly separated control from IUGR brain tissue samples, revealing the potential to develop predictive biomarkers. Moreover birth weight and metabolite intensity correlations indicated that the extent of alterations was dependent on the severity of IUGR.
Conclusions:
IUGR leads to metabolic alterations in the fetal rabbit brain, involving neuronal viability, energy metabolism, amino acid levels, fatty acid profiles and oxidative stress mechanisms. Overall findings identified aspargine, ornithine, N-acetylaspartylglutamic acid, N-acetylaspartate and palmitoleic acid as potential metabolite candidates to develop clinical biomarkers for the perinatal diagnosis of IUGR related abnormal neurodevelopment.
