Semester

Fall

Date of Graduation

2022

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Not Listed

Committee Chair

Mark Olfert

Committee Co-Chair

Timothy Nurkiewicz

Committee Member

Timothy Nurkiewicz

Committee Member

Paul Chantler

Committee Member

Melissa Blank

Committee Member

Kristin Ashford

Abstract

Electronic cigarette (e-cig) use is increasing due to aggressive marketing, tempting flavors, and seemingly higher acceptability in the community (lesser perceived social stigma) despite unproven claims of safety. In an alarming trend, pregnant women smokers have turned to novel “modified risk” products, such as e-cigs, in response to heavy marketing of e-cigs as safer alternatives to cigarettes and a tool to help quit smoking. This is despite proven detrimental effects of nicotine on a growing fetus, and scarcity of information regarding toxicity of e-liquid (with and without nicotine) on child development. Moreover, rampant e-cig use among youth (nearly 4 million in 2018, CDC) reflects a growing population of experienced and addicted female users who may become pregnant. This project addresses this emerging public health issue by providing information regarding consequences of maternal e-cig use and its long-term effects on child health outcomes.

It is established that both mother and fetus are vulnerable to environmental exposures during pregnancy. Prenatal exposure to nicotine leads to preterm births and is linked to adverse health, behavioral and cognitive outcomes in newborns. E-cigs have been shown to deliver physiologically significant amounts of nicotine to its users. Currently, little is known about the effects of e-cig use on perinatal and developmental outcomes and whether adverse effects can be attributed to nicotine delivery alone. Given the paucity of data, this overall goal project seeks to elucidate the impact of maternal e-cig use during pregnancy using an animal model to test cardiovascular and behavioral outcomes.

The first objective of this work was to determine dose-dependent effects of maternal e-cig exposure on functional vascular outcomes in conduit and resistance vessel beds and to investigate potential pathways that lead to this impairment. The second objective is to evaluate the effect of on cognitive development and behavioral deficits in the pups and compare between levels of exposure. The hypothesis is that 1) maternal e-cig exposure will lead to increased arterial stiffness and reduced vascular reactivity in aorta and middle cerebral artery, and this impairment will be at least partially mediated by the nitric oxide pathway; and 2) pups exposed to e-cig aerosol in utero will demonstrate hyperactivity, exploratory behavior, and impaired spatial and aversive learning as well as impaired memory.

The specific aims are to (1) determine dose-dependent effect of maternal e-cig vapor exposure (with and without nicotine) on arterial stiffness and vascular reactivity in offspring and (2) evaluate cognitive development and behavioral changes in pups exposed to e-cig vapor in utero using a battery of tests to tap different functional domains of learning and memory.

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