Semester

Spring

Date of Graduation

2022

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Physiology, Pharmacology & Neuroscience

Committee Chair

Stanley Hileman

Committee Co-Chair

Timothy Nurkiewicz

Committee Member

Timothy Nurkiewicz

Committee Member

Salik Hussain

Committee Member

Eric Kelley

Committee Member

Robert Dailey

Abstract

Nano-titanium dioxide (nano-TiO2) is a commonly utilized engineered nanomaterial found ubiquitously in consumer products. While benefits of ENM utilization in are undeniable, nanoparticle inhalation has been linked to cardiovascular consequences and altered microvascular responses. Given these outcomes, it is important to explore vulnerable timepoints, such as gestation, as robust vascular adaptations are essential for maternofetal health.

The first aim of this dissertation was to assess myogenic responsiveness following maternal nano-TiO2 inhalation. Fetal aortic responses were evaluated on gestational day (GD) 20 to assess how exposure may impact the F1 generation. Myogenic responsiveness within the uterine radial arteries were unaffected. Endothelium-dependent relaxation was found to be reduced within the fetal aortas of the exposure group.

The second aim was to evaluate the window of gestation that is most susceptible to maternal exposure. Exposure groups were divided into early (EE), mid (ME) and late (LE) and uterine radial artery responses were assessed on GD 20. The EE group showed increased sensitivity to Ang II and exhibited decreased protein level of angiotensin II type 2 receptor. EE resulted in reduced pup mass and placental efficiency, suggesting Ang II vasoconstriction may play a role in poor perfusion, resulting in reduced pup size.

The third aim was to further evaluate the susceptible time-point of gestational exposure by assessing placental physiology. Placental hemodynamics were not influenced by exposure, nor were Ang II receptor protein level, suggesting that the reduced pup mass within the EE group may be dependent upon uterine vascular function and not placental hemodynamics.

Included in

Physiology Commons

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