Fetal malnutrition and cigarette smoke exposure impair lung development in newborn mice

Our study aimed to investigate the impact of maternal protein restriction and gestational cigarette smoke exposure on lung development, inflammation, and redox balance in newborn mice. Pregnant C57BL/6 mice were divided into four groups: control (CG), protein restriction (PR), cigarette smoke (CS), and protein restriction with cigarette smoke (PRCS). Animals were subjected to a low-protein diet and/or cigarette smoke exposure during gestation. Male offspring were evaluated 24 hours after birth for biometric parameters, lung structure, inflammatory, oxidative stress, and extracellular matrix markers. The association between PR and CS exposure resulted in reduced body and lung mass, which indicated impaired growth biometric data. Morphometric analysis revealed increased alveolar airspace and reduced septal density, suggesting disrupted alveolarization. PR and CS modulated inflammatory responses, with increased expression of NF-κB, IL-1β, CCL-2, TNF-α, and leptin, alongside elevated VEGF and IL-10 levels. Oxidative stress was evidenced by increased SOD and CAT activities as well as elevated lipid peroxidation. Our findings demonstrate that maternal PR associated with CS exposure disrupts lung development and promotes early-life pulmonary inflammation and redox imbalance in male offspring. This study highlights the importance of maternal environmental factors during gestation and their implications for neonatal lung development.