425 - Maternal Electronic Cigarette Vaping During Pregnancy and Lactation Induces Asthma in Rat Offspring

Poster Number: 425
Publication Number: 425.429

Celia Yu, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, United States; Jie Liu, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, United States; Ying Wang, The Lundquist Institute, Torrance, CA, United States; Reiko Sakurai, The Lundquist Institute, Torrance, CA, United States; Amir Harb, The Lundquist Institute, Torrance, CA, United States; Virender K. Rehan, Harbor-UCLA Medical Center, Torrance, CA, United States

Background: A sharp increase in the use of electronic cigarettes (e-cig), including by pregnant women, exposes an increasing number of fetuses to potentially harmful e-cig constituents with little knowledge of its repercussions. We have previously shown that perinatal nicotine-induced asthma is associated with downregulation of PPARγ signaling and upregulation of Wnt signaling in the developing lung.  The impact of perinatal nicotine exposure via maternal vaping on the developing lung is unknown.

Objective: Determine the effect of perinatal maternal e-cig vaping on offspring pulmonary function and molecular markers of airway contractility.

Design/Methods: Pair-fed pregnant rat dams received saline, vehicle (e-cig without nicotine), or e-cig with nicotine daily from embryonic day 6 until postnatal day (PND) 21. Mimicking real life puffing topography, dams were exposed to 4-sec puff with one puff every 30s (puffing volume 35 ml), 3h/day, 7 days/week. Average maternal plasma nicotine level (7±4 ng/ml) using this vaping regimen is within the range observed in moderate cig smokers. Pups delivered spontaneously and breastfed ad libitum, but were not exposed to e-cig aerosols directly at any time. At PND21, lung resistance and compliance were determined following methacholine challenge. At sacrifice on PND21, lungs were collected and molecular markers of airway structure and contractility [α-smooth muscle actin (SMA), Calponin, Fibronectin, Collagen I/III], and key Wnt/PPARγ signaling intermediates were determined by qRT-PCR, immunoblotting, and immunostaining.

Results: Compared to controls, e-cig exposure resulted in a significant increase in airway resistance and a significant decrease in airway compliance. mRNA levels of Collagen III and LEF-1 increased, and those of PPARγ and ADRP decreased in the e-cig exposed group. Immunoblotting analysis showed that in the e-cig exposure group, protein levels of airway contractility markers (α-SMA, Calponin, Fibronectin, and Collagen I/III) and those of Wnt signaling intermediates (β-catenin and LEF-1) increased; levels of nicotinic acetylcholine receptors α3/α7 also increased. In contrast, PPARγ, which interacts directly with Wnt signaling intermediates, decreased compared to saline and vehicle groups. These data were confirmed by immunostaining of whole lung sections. Conclusion(s): Our data support increased predisposition to offspring asthma following perinatal maternal e-cig vaping and demonstrate the likely molecular mechanisms involved. These data add to the accumulating evidence contradicting the idea that e-cigs are"safe" or "safer" than traditional cigarettes.
Celia_Yu_CVCelia Yu_CV_2022-01-07.pdf