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Updated: Apr 27, 2026
Transuterine Fetal Tracheal Occlusion Model in Mice
Published on: February 5, 2021
Evidence for decreased lipofibroblast expression in hypoplastic rat lungs with congenital diaphragmatic hernia
Florian Friedmacher1, Naho Fujiwara, Alejandro Daniel Hofmann
1National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland, florian.friedmacher@gmx.de.
Insights
Congenital diaphragmatic hernia (CDH) in newborns is linked to reduced lipid-containing interstitial fibroblasts (LIFs) and adipocyte differentiation-related protein (ADRP) in developing lungs, potentially causing pulmonary hypoplasia (PH). This study confirms decreased LIF and ADRP expression in a rat model of CDH-induced PH.
Area of Science:
- Developmental biology
- Pulmonary medicine
- Cell biology
Background:
- Pulmonary hypoplasia (PH) is a severe complication of congenital diaphragmatic hernia (CDH) in newborns.
- Lipid-containing interstitial fibroblasts (LIFs) are crucial for fetal lung maturation, alveolarization, and lipid homeostasis.
- Adipocyte differentiation-related protein (ADRP) is a marker for LIFs and is highly expressed in fetal lungs during critical development stages.
Purpose of the Study:
- To investigate LIF expression in hypoplastic rat lungs in a nitrofen-induced CDH model.
- To assess ADRP expression and lipid content in lungs affected by CDH-associated PH.
- To determine if reduced LIF expression correlates with impaired lung development in CDH.
Main Methods:
- Rats were exposed to nitrofen or vehicle on embryonic day 9.5.
- Fetal lungs were collected at embryonic days 18.5 and 21.5 for analysis.
- Quantitative real-time PCR, immunohistochemistry, and oil red O staining were used to measure ADRP expression and lipid content.
Main Results:
- ADRP mRNA and protein expression were significantly reduced in CDH-associated PH lungs.
- Lipid content was markedly diminished in the alveolar mesenchymal cells of CDH-associated PH lungs.
- LIF expression was significantly decreased in the alveolar interstitium of CDH-associated PH lungs.
Conclusions:
- Decreased pulmonary LIF expression in late gestation suggests impaired LIF function in the nitrofen-induced CDH model.
- This impairment may disrupt fetal alveolarization and lipid homeostasis, contributing to PH development.
- Findings highlight the role of LIFs in lung development and their potential involvement in CDH pathophysiology.
Purpose:
Pulmonary hypoplasia (PH) is a serious condition in newborns with congenital diaphragmatic hernia (CDH). Lipid-containing interstitial fibroblasts (LIFs) play an essential role in fetal lung maturation by stimulating alveolarization and lipid homeostasis. In rodents, LIFs are first evident during the canalicular phase of lung development with a significant increase over the last 4 days of gestation. Adipocyte differentiation-related protein (ADRP), a functional lipogenic molecular marker characterizing LIFs, is highly expressed in fetal lungs during this critical time period. We hypothesized that LIF expression in hypoplastic rat lungs is decreased in the nitrofen-induced CDH model, which is accompanied by reduced alveolar ADRP expression and lipid content.
Methods:
On embryonic day 9.5 (E9.5), time-mated rats received either nitrofen or vehicle. Fetuses were sacrificed on selected time points E18.5 and E21.5, and dissected lungs were divided into controls and CDH-associated PH. Pulmonary gene expression levels of ADRP were determined by quantitative real-time polymerase chain reaction. ADRP immunohistochemistry and oil red O staining were used to assess pulmonary protein expression and lipid content. Immunofluorescence double staining for alpha smooth muscle actin, which is known to be absent in LIFs, and lipid droplets was performed to evaluate the pulmonary expression of this specific subset of fibroblasts.
Results:
Relative mRNA expression of ADRP was significantly reduced in lungs of CDH-associated PH on E18.5 and E21.5 compared to controls. ADRP immunoreactivity and lipid staining were markedly diminished in alveolar mesenchymal cells of CDH-associated PH on E18.5 and E21.5 compared to controls. Confocal laser scanning microscopy demonstrated markedly decreased LIF expression in alveolar interstitium of CDH-associated PH on E18.5 and E21.5 compared to controls.
Conclusion:
Decreased pulmonary LIF expression during late gestation suggests impaired LIF functioning in the nitrofen-induced CDH model, which may cause disruption in fetal alveolarization and lipid homeostasis, and thus contribute to the development of PH.
