Prenatal cannabinoid and nicotine exposure: senescence as a developmental origin of bronchopulmonary dysplasia?

The increasing use of cannabis during pregnancy, particularly in combination with nicotine-containing products, has emerged as an important public health concern. 1 , 2 While prenatal tobacco exposure has long been associated with impaired fetal growth and adverse respiratory outcomes, 3 , 4 the biological consequences of combined exposure to nicotine and cannabinoids on the developing human lung remain poorly understood. In this issue, El Alam and colleagues provide compelling mechanistic evidence that co-exposure to nicotine, tetrahydrocannabinol (THC), and cannabidiol (CBD) induces a senescence-like phenotype in the developing human fetal lung. 5 Their work introduces cellular senescence as a potentially important link between prenatal environmental exposures and later chronic lung disease, including bronchopulmonary dysplasia (BPD). This study is particularly timely because prenatal substance exposure is rapidly increasing. In many countries and regions where recreational cannabis use has become legalized or socially normalized, cannabis use during pregnancy has increased substantially, often in conjunction with tobacco products. 6 , 7 Importantly, pregnant women commonly perceive cannabis—particularly CBD-containing products—as relatively safe or “natural,” despite limited evidence regarding their safe use during pregnancy 8 , 9 and scant evidence supporting that they can be used safely during fetal development, especially with respect to pulmonary outcomes. The present study therefore addresses a critical gap in developmental lung biology. Recent studies further suggest that senescence in the immature lung is not uniformly detrimental but may also represent a physiologic developmental program which reveals that there is transient senescence during the early saccular stage which contributes to normal postnatal alveolarization, whereas persistent hyperoxia-induced senescence later in development promotes alveolar and vascular simplification. 10 These observations highlight the importance of developmental timing and cellular specificity when determining whether senescence exerts adaptive or pathogenic effects within the developing lung.