Altered uterine artery protein signature and function following E-cigarette exposure in pregnancy.

OBJECTIVE: Over the past decade e-cigarette (e-cig) usage has become a growing public health concern, especially during pregnancy as many perceive e-cigs as a safer alternative to combustible cigarettes. Although human and animal models exhibit altered uterine artery Doppler velocimetry and waveform abnormalities following traditional smoking and buccal nicotine exposure, the effects of e-cig aerosols on pregnancy are incompletely researched and understood. We hypothesized that an altered uterine artery proteomic signature, accompanied by functional deficits, will be caused by e-cig vaping during pregnancy. METHODS: In a validated timed pregnant Sprague-Dawley rat model system, a custom-engineered vaping system comprising a commercial atomizer and vape unit was utilized to generate and deliver e-cig aerosols that mimic the aerosols produced by commercial e-cigs, once daily, to pregnant dams. RESULTS: Mean fetal weight, crown-rump length, and placental weight were significantly lower in the E-Cig group than those in the pair-fed Control group. Mass spectrometry followed by proteomic analysis detected a total of 2129 proteins; 36 significantly altered proteins were mostly related to immune system and vasodilation. Principal component analysis validated the protein signature. The uterine arteries of e-cig exposed rats demonstrated impaired concentration-dependent acetylcholine-induced uterine artery relaxation. Supplementation of N(ω)-nitro-L-arginine methyl ester (L-NAME) confirmed a role for the nitric oxide (NO) system. Immunofluorescence validated the localization to the uterine artery endothelium and the decreased levels of vasodilatory excitatory P-Ser(1177) endothelial NO synthase. CONCLUSIONS: Identifying the pathway(s) involved in the pathogenesis of uterine artery dysfunction creates a potential for pinpointing antagonistic and/or reversal medications, thereby preventing or reducing e-cigarette mediated uteroplacental dysfunction and fetal growth restriction.