Early-life ozone exposure modulates region-specific gene expression in the developing rat lung

Area of Science:

• Environmental toxicology
• Developmental biology
• Molecular genetics

Background:

• Early-life exposure to environmental pollutants like ozone can impair lung development.
• The specific molecular pathways affected by early-life ozone exposure remain largely unknown.

Purpose of the Study:

• To investigate gene expression changes in rat lungs following early-life episodic ozone exposure.
• To identify molecular mechanisms underlying ozone-induced alterations in lung development.

Main Methods:

• Rat pups were exposed to ozone or filtered air from postnatal day 7 to 28.
• Lung tissues were microdissected and analyzed using RNA-Sequencing (RNA-Seq) at juvenile and adult stages.
• Gene expression patterns were compared between ozone-exposed and control groups, and between different lung regions.

Main Results:

• Ozone exposure altered inherent gene expression differences between lung regions in both sexes.
• Statistically significant ozone-attributed gene expression changes were primarily observed in female rats.
• In juvenile females, 355 differentially expressed genes were found between distal airways and parenchyma, including those involved in epithelial-to-mesenchymal transition and cell growth.

Conclusions:

• Episodic early-life ozone exposure can lead to sex-specific alterations in lung gene expression.
• Ozone-induced changes in genes related to epithelial-to-mesenchymal transition and cell growth suggest impacts on lung morphogenesis and development.
• This study provides novel molecular targets for understanding ozone's effects on lung development.