Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor

Dr. Daniel B. Hardy

Abstract

Nicotine exposure during pregnancy leads to adverse health outcomes, including compromised placental development. Although the molecular mechanisms remain elusive, recent studies identified that endoplasmic reticulum (ER) stress may underlie poor placentation. Therefore, we were interested in investigating the effects of nicotine exposure on the ER stress response in the placenta. A well-established maternal nicotine exposure rat model and Rcho-1 trophoblast giant cell model were utilized to address the research questions. Maternal nicotine exposure in vivo led to elevated ER stress in association with impaired disulfide bond formation and hypoxia. Nicotine exposure in vitro further differentiated that ER stress may be augmented directly through nicotinic acetylcholine receptor activation and indirectly through nicotine-induced hypoxia. Moreover, we relieved nicotine-induced ER stress in Rcho-1 cells in vitro using Tauroursodeoxycholic acid. In conclusion, this thesis provides novel mechanistic insight and contributes to the development of innovative therapeutic approaches to ameliorate nicotine-induced injury in pregnancy.