Semester

Fall

Date of Graduation

2018

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Physiology, Pharmacology & Neuroscience

Committee Chair

Robert Brock

Committee Co-Chair

Jesus Araujo

Committee Member

Jesus Araujo

Committee Member

William Stauber

Committee Member

Christopher Cuff

Committee Member

Aaron Erdely

Committee Member

Stephen Valentine

Abstract

Titanium dioxide nanoparticles (nano-TiO2) are one of the most widely used engineered nanomaterials (ENM). Their ubiquitous inclusion warrants a more thorough understanding of their toxicity, particularly in sensitive populations such as pregnant women and the developing fetus.

The aim of the first study was to determine the most sensitive segments of the vasculature to pulmonary ENM exposure. Macrovascular function was investigated in the thoracic aorta, common femoral artery and 3rd order mesenteric arterioles using wire myography. Microvascular function was assessed in 4th and 5th order mesenteric arterioles via pressure myography. Nano-TiO2 exposure induced impairments in endothelium-dependent and -independent relaxation in the macrovasculature and dysfunction in the microvasculature. Interestingly, this dysfunction was more robust in the microvessels.

The aims of the second study were: 1) to investigate the uterine microvascular repercussions of pulmonary ENM exposure, 2) to identify the role played by innate lymphoid cells in the inflammatory response to acute nano-TiO2 exposure. This study proposes that group II innate lymphoid cells respond within 4 hours to damage-associated molecular patterns from lung epithelial and innate immune cells in response to intratracheal instillation of nano-TiO2. Furthermore, impairment of endothelium-dependent dilation of the uterine radial arterioles was identified 24 hours post-exposure.

Study 3 aimed to determine the effects of gestational nano-TiO2 exposure on the maternal-fetal circulation. Based on previous research, we predicted that gestational nano-TiO2 inhalation exposure would increase placental vascular resistance and impair endothelium-dependent and -independent dilation of the umbilical microvasculature.

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