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Effect of maternal food restriction on fetal rat lung lipid differentiation program
Ahmet Karadag1, Reiko Sakurai, Ying Wang
1Department of Pediatrics, Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute at Harbor-UCLA, David Geffen School of Medicine at UCLA, Torrance, California 90502, USA.
Insights
Maternal food restriction (MFR) in rodents alters offspring lung structure and lipid programming. These changes impact alveolar development and lipid accumulation, suggesting potential for targeted interventions.
Area of Science:
- Pulmonary Medicine
- Developmental Biology
- Nutritional Science
Background:
- Intrauterine growth restriction (IUGR) effects on fetal lung development are not well understood.
- Maternal food restriction (MFR) is a model for IUGR, impacting offspring development.
- Limited data exists on pulmonary consequences of IUGR.
Purpose of the Study:
- To investigate the impact of maternal food restriction (MFR) on offspring lung structure and lipid differentiation.
- To analyze lung development in offspring exposed to MFR during gestation.
- To identify molecular pathways affected by MFR in the developing lung.
Main Methods:
- Rodent model of 50% MFR from day 10 of gestation.
- Assessment of lung morphology, Western blotting, RT-PCR, and Oil Red O staining.
- Analysis at postnatal days 1, 21, and 9 months.
Main Results:
- MFR offspring showed altered lung structure with decreased alveolar number and increased septal thickness.
- Lung lipid accumulation was decreased at postnatal day 1 but increased by 9 months in MFR offspring.
- Significant temporal changes observed in parathyroid hormone-related protein/peroxisome proliferator-activated receptor gamma signaling and surfactant synthesis.
Conclusions:
- Maternal food restriction significantly alters fetal lung morphometry and lipid differentiation programming.
- Specific epithelial-mesenchymal signaling pathways are affected by MFR, influencing lung development.
- Findings suggest potential for interventions to mitigate adverse pulmonary effects of IUGR.
Abstract:
Although "fetal programming" has been extensively studied in many organs, there is only limited information on pulmonary effects in the offspring following intrauterine growth restriction (IUGR). We aimed to determine the effects of nutrient restriction on the lung structure and lung lipid differentiation programs in offspring using an animal mode of maternal food restriction (MFR). We utilized a rodent model of 50% MFR from day 10 of gestation to term and then using lung morphology, Western blotting, Real Time RT-PCR and Oil Red O staining, lung structure and development of the offspring were examined at postnatal days (p) 1, p21, and 9 months (9M). At postnatal day 1, MFR pups weighed significantly less compared to control pups, but at p21 and 9M, they weighed significantly more. However, lung weight, expressed as a percentage of body weight between the two groups was not different at all time-points examined. The MFR group had significantly decreased alveolar number and significantly increased septal thickness at p1 and 9M, indicating significantly altered lung structure in the MFR offspring. Furthermore, although at p1, compared to the control group, lung lipid accumulation was significantly decreased in the MFR group, at 9M, it was significantly increased. There were significant temporal changes in the parathyroid hormone-related protein/peroxisome proliferator-activated receptor gamma signaling pathway and surfactant synthesis. We conclude that MFR alters fetal lung lipid differentiation programming and lung morphometry by affecting specific epithelial-mesenchymal signaling pathways, offering the possibility for specific interventions to overcome these effects.
