Effect of maternal food restriction on fetal rat lung lipid differentiation program.
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.
Karadag
Ahmet
A
Department 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.
Sakurai
Reiko
R
Wang
Ying
Y
Guo
Pinzheng
P
Desai
Mina
M
Ross
Michael G
MG
Torday
John S
JS
Rehan
Virender K
VK
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005325:Fetal Organ Maturity; D008168:Lung / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D008563:Membrane Lipids / Q000096:biosynthesis*; D047495:PPAR gamma / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D011650:Pulmonary Alveoli / Q000196:embryology / Q000473:pathology*; D011663:Pulmonary Surfactants / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
D008563:Membrane Lipids; D047495:PPAR gamma; D044162:Parathyroid Hormone-Related Protein; D011663:Pulmonary Surfactants