Adverse early-life environment impairs postnatal lung development in mice

Area of Science:

• Developmental biology
• Pulmonary medicine
• Environmental health

Background:

• Fetal growth restriction (FGR) is a significant risk factor for bronchopulmonary dysplasia (BPD).
• Maternal stress and poor nutrition are associated with FGR.
• The impact of perinatal stress on fetal lung development is not well understood.

Purpose of the Study:

• To investigate the effects of an adverse early life environment (AELE) on lung development in a murine model.
• To test the hypothesis that maternal exposure to perinatal stress and a Western diet impairs offspring lung development.

Main Methods:

• A murine model was used, exposing female mice to a Western diet and perinatal environmental stress (AELE) before conception.
• Offspring lungs were analyzed at postnatal day 21 and in adulthood (8-14 weeks).
• Analyses included histology, gene expression, microRNA profiling, and protein analysis.

Main Results:

• AELE led to increased mean linear intercept and decreased radial alveolar count and secondary septation in offspring lungs.
• Capillary counts were reduced in both juvenile and adult AELE mice.
• AELE altered protein levels of key growth factors (VEGFA, VEGFR2, eNOS, HIF-1α) and affected DNA methylation and microRNA expression.

Conclusions:

• AELE causes persistent impairment of lung alveolar and vascular growth from juvenile to adult stages.
• These lung development deficits remain even after normalizing diet and environment post-weaning.
• AELE alters gene expression related to lung remodeling.