ELECTRONIC CIGARETTE VAPING & VASCULAR SEQUELAE IN THE UTERUS DURING PREGNANCY Despite serious pregnancy complications, 50% of women who use tobacco products will continue to do so during pregnancy. A recent 2017 study estimates as many women use electronic-cigarettes (e-cigs) as conventional cigarettes during pregnancy. One major reason for this alarming data is that traditional tobacco users view vaping during pregnancy as a “safer” alternative. However, e-cig vapor reveals a myriad of chemicals which may be harmful to both the mother and the fetus. Using our well-established pregnant rat model, we obtained preliminary data utilizing a state-of-the-art custom-engineered e-cig atomizer that offered a translational inhalation delivery method and generated vapor profiles directly comparable to human vaping. The preliminary data demonstrated e-cig-induced major fetal growth deficit and provides the first evidence for impaired gestational circulatory adaptations including uterine blood flow, the prime regulator of gas and nutrient delivery from mother to fetus. Aim#1 will test if vaping e-cig base (varying ratios of propylene glycol: glycerol) alone or with increasing doses of nicotine produce a dose- dependent effect on uterine blood flow (UBF) and fetal growth response. Further, we will test if there are e-cig- induced systemic cardiovascular adaptations during pregnancy. We will assess maternal reproductive vascular, and e-cig-induced fetal cardiovascular adaptations, accompanied by effects on the pulmonary system utilizing high frequency ultrasonography, flexiVent, TTE, ECG, Luminex xMAP technology, and surgical catheterization for blood pressure and microsphere-based flow assessment. Aim#2 will test if vaping e-cig will impair uterine artery relaxation via the endothelium-derived NO vs. EDHF vs. PGI2 pathways (the three vasodilators that entirely regulate primary uterine artery blood flow in pregnancy). We will pharmacologically block combinations of endothelial-derived vasodilator pathways using pressure arteriography, and dissect impaired cell signaling utilizing HPLC, histological approaches, immunoblotting, and other molecular tools. Our proposal explores a new frontier of gestational research developing the first mechanistic framework for e-cig vaping-induced uterine circulatory adaptations in a model that offers a translational inhalation delivery and vapor profiles comparable to human vaping. The proposed studies on the health effects of e-cigs during pregnancy will facilitate applicable policy implementation on potential risks these devices pose to the public. Proposed studies directly address a key consensus recommendation of the most recent NIH/NHLBI workshop on cardiovascular disease and the emergence of e-cigs, i.e. investigating effects of e-cigarette aerosol exposure in pregnant women.

Narrative The U.S. Surgeon General recently announced the use (vaping) of electronic cigarettes (e-cigs) as a major public health concern. Utilizing a state-of-the-art custom-engineered vaping system with an atomizer identical to those sold in vape shops world-wide, the proposed studies discerning the health effects of e-cigs during pregnancy will allow effective education of the public and will facilitate applicable policy implementation regarding the potential risks these devices pose to the public. The proposed studies directly address a stated consensus recommendation of the most recent NIH/NHLBI workshop on cardiovascular disease and the emergence of e-cigs, i.e. investigating effects of e-cigarette aerosol exposure in pregnant women.