Maternal Tobacco Smoke Exposure Alters Elastin Splicing at Exon 7 and 34 in the Lung of Rat Pups

Abstract

Maternal tobacco smoke (MTS) exposure reduces offspring lung function in humans and animal models. We showed that MTS increases static lung compliance in female, but not male, rat pups. Lung function depends on expression of alternatively spliced elastin transcripts. Using RNA‐seq, we identified alternative splicing at exons 7 and 34 of elastin transcripts in the immature rat lung. We hypothesized that levels of exon 7‐ and 34‐containing elastin transcripts would vary with lung development in male and female rat lung, and with MTS exposure, in female rat lung.Pregnant rats were exposed to tobacco smoke (MTS) or room air (Control) and pups killed at term birth (d0‐immature lung), or cross‐fostered to a control dam and killed at day of life 21 (d21‐mature lung). We measured elastin mRNA transcripts that contained exon 7 (E+7) and exon 34 (E+34). (n=5/group).Results: Between d0 and d21, lung E+7 decreased in control female (46±15%*) and male (61±14%*) rats, while E+34 increased in female (140±28%*) and was unchanged in male rats. Compared to age‐and sex‐matched controls, in females, MTS decreased E+7 at d0 (16±2%*), and increased E+7 at d21 (589±176%*). Similarly, in female pups, MTS decreased E+34 at d0 (25±16%*), and increased E+34 at d21 (200±51%*). In male lung, MTS did not affect levels of E+7 at d0, but increased E+7 at d21 (462±85%*). MTS did not affect E+34 in males. *p<0.05ConclusionsExon 7‐ and 34‐containing elastin transcripts in rat lung are developmentally regulated and sex‐specifically altered by MTS. We speculate that MTS‐induced differences in elastin alternative splicing during development may alter lung function and structure through disruption of the timing and integrity of elastic fiber assembly in the rat.*Funding: APS and NHLBI; 1 R25 HL115473‐01